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Agarwal, Udit. "Factors Affecting Ventricular Remodeling Post Myocardial Infarction." Kent State University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=kent1269627876.
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McDevitt, Todd C. "Spatially controlled engineering of myocardial tissue /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/8090.
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Krimpen, Cornelis van. "Cardiac remodeling and angiotensin II after an experimental myocardial infarction." Maastricht : Maastricht : Rijksuniversiteit Limburg ; University Library, Maastricht University [Host], 1991. http://arno.unimaas.nl/show.cgi?fid=5677.
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Daniels, Christopher Ray. "Extracellular Ubiquitin: Role in Cardiac Myocyte Apoptosis and Myocardial Remodeling." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etd/2341.
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Activation of sympathetic nervous system is a key component of myocardial remodeling that generally occurs following ischemia/reperfusion (I/R) injury and myocardial infarction. It induces cardiac myocyte apoptosis and myocardial fibrosis, leading to myocardial dysfunction. Intracellular ubiquitin (UB) regulates protein turnover by the UB-proteosome pathway. The biological functions of extracellular UB in the heart remain largely unexplored. Previously, our lab has shown that β-adrenergic receptor (β-AR) stimulation increases extracellular UB levels, and extracellular UB inhibits β-AR-stimulated apoptosis in adult rat ventricular myocytes (ARVMs). This study explores the role of extracellular UB in myocyte apoptosis, fibroblast phenotype and function, and myocardial remodeling following β-AR stimulation and I/R injury. First, left ventricular (LV) structural and functional remodeling was studied 7 days after chronic β-AR-stimulation in the presence or absence of UB infusion. Echocardiographic analyses showed UB infusion decreases β-AR-stimulated increases in percent fractional shortening and ejection fraction. It decreased cardiac myocyte apoptosis and myocardial fibrosis. UB activated Akt, and inhibition of Akt inhibited β-AR-stimulated increases in matrix metalloproteinase-2 expression. Second, using cardiac fibroblasts, we provide evidence that extracellular UB interacts with the cell surface and co-immunoprecipitates with CXCR4. UB treatment increased expression of α-smooth muscle actin (myofibroblast marker), and induced rearrangement of actin into stress fibers. It inhibited lamellopodia and filopodia formation, and cell migration into the wound. Third, using isolated mouse heart and I/R injury as a model, we provide evidence that UB treatment decreases I/R-mediated increases in infarct size. UB treatment improved functional recovery of the heart as measured by increased % LV developed pressure. Activation of proapoptotic proteins, p-STAT-1 and caspase-9, was significantly lower in UB I/R hearts versus I/R alone. In ARVMs, UB treatment decreased simulated I/R-induced apoptosis. It activated Akt (anti-apoptotic kinase) and inhibited activation of GSK-3β (pro-apoptotic kinase). It decreased I/R-induced oxidative stress and protected anoxia-induced mitochondrial polarization. In fibroblast and ARVMs, CXCR4 antagonism negated the effects of UB, while mutated UBs (unable to interact with CXCR4) had no effect. Thus, extracellular UB, most likely acting via CXCR4, modulates myocardial remodeling with effects on heart function, fibroblast phenotype and function and myocyte apoptosis.
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Атаман, Юрій Олександрович, Юрий Александрович Атаман, Yurii Oleksandrovych Ataman, O. A. Vorozhko, and O. S. Voloshin. "Structural and functional features of myocardial remodeling in professional athletes." Thesis, Сумський державний університет, 2018. http://essuir.sumdu.edu.ua/handle/123456789/71676.
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Shao, Qiming. "Membrane remodeling in heart failure due to myocardial infarction in rats." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq23662.pdf.
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Liao, Songyan, and 廖松岩. "Novel therapies for prevention of left ventricular remodeling following myocardial infarction." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197141.
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Heart failure (HF) following myocardial infarction (MI) is the leading cause of mortality and morbidity worldwide. Existing medical and interventional therapies can only reduce the cardiomyocytes (CMs) lost during MI. They are unable to replenish the permanent loss of CMs and this contributes to progressive pathological left ventricular (LV) remodeling and HF. Cell-based therapies using adult stem cells or embryonic stem cells (ESCs) and their cardiac derivatives have frequently been explored as a potential therapeutic approach to restore cardiac function in HF. The objectives of this thesis are to evaluate the efficacy and safety of different approaches of stem cell based therapy to improve cardiac function using small and large animal MI models.
In Chapter 3, we studied the functional consequences of direct intramyocardial transplantation of ESCs and ESC-derived cardiomyocytes (ESC-CMs) in a murine model of acute MI. LV ejection fraction (LVEF) and maximal positive or negative pressure derivative (dP/dt) improved 4 weeks after transplantation of either ESCs or ESC-CMs. Nevertheless there was a higher incidence of inducible ventricular tachyarrhythmia (VT) and higher mortality in animals transplanted with ESC-CMs than those with ESCs. At a single cell level, ESC-CMs exhibited immature electrophysiological properties such as depolarized resting membrane potential (RMP), longer action potential duration (APD) and automaticity.
In Chapter 4, we tested the hypothesis that genetic modification of these immature electrophysiological properties of ESC-CMs by overexpression of Kir2.1 gene encoding the ion channels for IK1, may alleviate the pro-arrhythmic risk. In this study, Kir2.1 channels expression could be controlled with the administration of doxycycline (DOX). The DOX-treated ESC-CMs were more mature with hyperpolarized RMP and shorter APD than their counterparts without DOX treatment. A similar improvement in LV systolic function was observed 4 weeks after both DOX treated and untreated ESCCMs transplantation, although those animals transplanted with DOX-treated ESC-CMs had a significantly lower incidence of spontaneous and inducible VT. Histological analysis in both studies suggested that the major mechanisms of improvement in cardiac function were related to angiogenesis and low apoptosis rate of native cardiomyocytes mediated via paracrine effects. Importantly, very limited retention of ESC-CMs was observed 4 weeks after transplantation.
Cell-based patches that use different bioengineering techniques have been proposed to improve cell retention and survival following transplantation. In Chapter 5, the efficacy of a passive epicardial patch was tested in a chronic large animal MI model with HF created with catheter-based coronary embolization. The implantation of an epicardical patch over the infarcted LV region was performed 8 weeks after MI in pigs with impaired LVEF. At week 20, pigs implanted with epicardical patches had significantly thicker LV wall thickness at the infarction sites, smaller LV dilation and better LV systolic function compared with control animals. The expression of MMP-9 was significant lower in the epicardical patch group at the peri-infarct zones. These findings suggested that a passive epicardial patch can improve LV function in HF and provides important proof-of-principle data to support its use as a platform for delivery of cell-based therapies after MI.published_or_final_version
Medicine
Doctoral
Doctor of Philosophy
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Chaggar, Parminder. "Plasma cytokines and markers of remodeling in myocardial injury and repair." Thesis, University of Manchester, 2018. https://www.research.manchester.ac.uk/portal/en/theses/plasma-cytokines-and-markers-of-remodeling-in-myocardial-injury-and-repair(ea82d837-8825-4f1e-ac75-890458294eff).html.
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Introduction: The heart failure (HF) phenotype is associated with multiple pathological changes at the cellular/biochemical level but this is not always a permanent state, despite sometimes extremely severe clinical and echocardiographic features. However, the underlying molecular and inflammatory processes are incompletely understood and often, contradictory effects are reported. This study examines a wide array of plasma pro-inflammatory markers and remodeling proteins in experimentally induced HF and recovery. Methods: Plasma IFNÎ3, CXCL-9, IP-10, IL-21, IL-17A, TNFα, decorin, sFRP-3 and VEGF-A patterns were assessed in a series of ovine models; 8 sheep that underwent tachypaced-induced HF and recovery with cessation of pacing (Recovery group); 7 sheep that underwent tachypaced-induced asymptomatic LV dysfunction and subsequent treatment with tadalafil to prevent clinical deterioration in the context of continued tachypacing (Tadalafil sheep); and 5 sheep that underwent acute myocardial ischaemia-reperfusion injury (MI group). Baseline inflammatory profiles and remodeling proteins were validated in a separate cohort of 10 healthy sheep that underwent a comprehensive frailty assessment. Results: There was a borderline inverse association between IFNÎ3 with clinical HF in the Recovery group but no correlation with LV function. High baseline levels of pro-inflammatory cytokines did not impact on susceptibility to, severity of, or recovery from HF in sheep exposed to tachycardic pacing. Furthermore, plasma decorin increases significantly with tachypaced-HF and remains elevated despite improved LV function or tadalafil treatment. Conclusion: The present study has examined a broad inflammatory profile in HF and recovery, including those mediated via TH1 (IFNÎ3, CXCL-9 and IP-10), TH2 (IL-21), TH17 (IL-17A) and monocyte (TNFα) cell lineages. The findings demonstrate that systemic inflammation has no impact on susceptibility to, severity of, or recovery from HF in sheep exposed to tachycardic pacing. The findings of this study may draw into question whether the immune system plays a pivotal role in HF disease progression and severity although further research is required before definitive conclusions can be secured. Furthermore, this study demonstrates plasma decorin increases significantly with the development of HF. This may represent a physiological response to attenuate the effects of adverse remodeling in HF. This is the first study to demonstrate temporal changes in plasma decorin during both myocardial injury and recovery in a large mammal. Decorin may serve as a biomarker of myocardial injury and could be a target for therapeutic manipulation. These findings require validation in a larger series.
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Singh, Mahipal, Cerrone R. Foster, Suman Dalal, and Krishna Singh. "Osteopontin: Role in Extracellular Matrix Deposition and Myocardial Remodeling Post-MI." Digital Commons @ East Tennessee State University, 2010. https://dc.etsu.edu/etsu-works/8576.
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Remodeling after myocardial infarction (MI) associates with left ventricular (LV) dilation, decreased cardiac function and increased mortality. The dynamic synthesis and breakdown of extracellular matrix (ECM) proteins play a significant role in myocardial remodeling post-MI. Expression of osteopontin (OPN) increases in the heart post-MI. Evidence has been provided that lack of OPN induces LV dilation which associates with decreased collagen synthesis and deposition. Inhibition of matrix metalloproteinases, key players in ECM remodeling process post-MI, increased ECM deposition (fibrosis) and improved LV function in mice lacking OPN after MI. This review summarizes — 1) signaling pathways leading to increased expression of OPN in the heart; 2) the alterations in the structure and function of the heart post-MI in mice lacking OPN; and 3) mechanisms involved in OPN-mediated ECM remodeling post-MI.
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McLaughlin, Sarah Joan Margaret. "Human Recombinant Collagen Hydrogel for Control of Ventricular Remodeling and Repair After Myocardial Infarction." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/42543.
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Myocardial infarction (MI) leads to permanent loss of cardiac muscle due to the limited regenerative potential of the mammalian heart. The affected heart muscle is replaced by a fibrotic scar; however, the scar is not able to offset the increase in wall stress placed on the remaining myocardium. This distending pressure can lead to dilative remodeling of the ventricle, progressive loss of cardiac function, and heart failure. Despite current medical therapy, heart failure continues to have a high mortality rate. Therefore, there is a clinical need for treatments that can both improve cardiac function post-MI and reduce ventricular remodeling to prevent progression to heart failure.
Injectable biomaterials aim to provide a scaffold to stimulate infarct repair by mimicking the healthy cardiac extracellular matrix (ECM). The ECM plays a critical role in tissue regeneration but after a MI it is pathologically modified. Injection of biomaterials post-MI can provide a scaffold that better stimulates infarct repair. In this study, hydrogels were developed from recombinant human type I and type III collagen (rHCI and rHCIII), the two most prevalent structural proteins in the cardiac ECM. Injection of rHCI and rHCIII hydrogels in a mouse model of MI improved cardiac function and reduced infarct size 28 days post-treatment. Infarcted hearts treated with rHCI exhibited improved myocardial salvage in the region bordering the scar with improved capillary density. rHCI hydrogel was also superior to rHCIII in reducing ventricular remodeling.
The injection of rHCI hydrogel into the border zone post-MI resulted in an acute improvement of contractile function two days after treatment that was maintained long-term. At two days post-injection, rHCI treated animals had reduced apoptotic cardiomyocytes and lower levels of oxidative stress. Methylglyoxal modifies and crosslinks collagen in the ECM, leading to oxidative stress. Two days after injection, the rHCI hydrogel at the epicardial surface was modified by methylglyoxal, while methylglyoxal-derived advanced glycation end-product levels in the underlying myocardium were lower than in control animals. It appears that rHCI hydrogel injection is soaking up free methylglyoxal from the myocardium, reducing levels of oxidative stress in cardiac muscle and improving contractility of cardiomyocytes bordering the scar. These results suggest that rHC therapy is a promising approach to improve cardiac contractility, and limit ventricular remodeling post-MI.
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Hunt, Darlene L. "Mechanisms of post-myocardial infarction healing from acute survival to chronic remodeling /." Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3368469.
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Thesis (Ph. D.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed August 25, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 85-101).
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Scofield, Stephanie. "Exogenous Ubiquitin: Role in Myocardial Inflammation and Remodeling Post- Ischemia/Reperfusion Injury." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etd/3347.
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Sympathetic stimulation occurs in the heart after injuries such as ischemia/reperfusion (I/R) and myocardial infarction and affects myocardial remodeling. Prolonged sympathetic stimulation can result in myocardial dysfunction through its effects on cardiac myocyte apoptosis and myocardial fibrosis. Ubiquitin (UB) is well known for its role of tagging old or damaged proteins for degradation via the UB-proteosome pathway. The role of exogenous UB however, is not fully understood. Previously, our lab showed that β-adrenergic receptor (β-AR) stimulation increased levels of extracellular UB in the conditioned media of adult rat ventricular myocytes and that UB inhibits β-AR-stimulated apoptosis. This study investigates the role of extracellular UB after myocardial I/R injury in terms of infarct size, function, inflammation and proteomic changes in vivo as well as the effects of extracellular UB on cardiac fibroblast function in vitro. First, we validated a method of consistently measuring real-time myocardial ischemia and reperfusion in vivo. Second, cardiac function was studied 3 days post I/R injury in the presence or absence of UB infusion. Echocardiographic analysis determined UB infusion increased cardiac function after I/R injury in terms of ejection fraction and fractional shortening. UB decreased infarct size and infiltration of inflammatory cells including neutrophils and macrophages as well as reduced activity of neutrophils. UB increased protein levels of matrix metalloproteinase (MMP)-2 and transforming growth factor-β1 and increased activity of MMP-9. Third, in adult rat primary cardiac fibroblasts, we demonstrate that extracellular UB interacts with CXCR-4. UB treatment decreased serum-mediated increases in fibroblast proliferation and enhanced the contraction of fibroblast-populated collagen gels. Thus, extracellular UB likely interacts with CXCR-4 to influence fibroblast function and proliferation. Additionally, UB influences cardiac remodeling in terms of heart function, infarct size, inflammatory response and proteomic profile.
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Lefnaier, Wafa. "Potential Role for the Sarcolemmal Membrane Associated Protein Isoform 3 (SLMAP3) in Cardiac Remodeling Post Myocardial Infarction." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/35713.
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ABSTRACT
The Sarcolemmal Membrane Associated Protein 3 (SLMAP3) is a tail-anchored membrane protein, which is ubiquitously expressed in tissues including myocardium. It is a component of subcellular membranes and the centrosome, and it appears to serve distinct roles in cell growth and membrane biology. In addition, mutations in SLMAP have been linked to Brugada syndrome, which leads to cardiac dysfunction and death. Here, we have examined the effects of different levels of SLMAP3 on postnatal heart function, pre and post myocardial infarction (MI).Transgenic (TG) mice with a cardiac specific expression of SLMAP3 isoform were generated and assessed with echocardiography to measure function, immunohistochemistry for histology, TUNEL assay for apoptosis, Masson’s trichrome staining for fibrosis, and Western blots for protein expression.
Baseline echocardiography of 8 weeks old TG mice showed a normal cardiac function that was expressed in ejection fraction percent (%EF=66%±7.42), which was similar to those of wild type mice (%EF=67%±9.36), p<0.05, n=20-25 (in each group). MI was induced by permanent ligation of left anterior descending (LAD) artery in 9 week old WT & TG mice, while sham was the control. No death was recorded in SLMAP3 TG mice up to one year post MI, whereas 70% of WT mice had deceased, p<0.01, n=17-18 (in each group). Cardiac function was assessed by echocardiography (at 4 week post MI) showed a partially restored ejection fraction percent (%EF~49.2%±17.02) in SLMAP3 TG mice post MI compared to (%EF~36.4%±15.25) in WT mice post MI, p<0.05, n=15-16 (in each group). Furthermore, infarct size (IS) as well as collagen area (CA) post MI were significantly attenuated (IS~43%±8.82, CA~35%±5.15) in SLMAP3 TG myocardium in comparison to WT (IS~53%±9.30, CA~47%±7.36), p<0.05, n=20- 22 (each group). Moreover, expression of the heart failure biomarker galectin3 was markedly
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attenuated (1.8±0.20) in SLMAP3 TG hearts post MI compared to (3.2±0.35) in WT, p<0.01, n=4-5 (in each group). The apoptotic index in SLMAP3 TG myocardium assessed by TUNEL was markedly decreased (77±11.48) in comparison to WT (112±15.32), p<0.05, (n=20-22 in each group). Further, expression of proapoptotic proteins (Caspase3 and Bax) was significantly attenuated in SLMAP3 TG (p<0.05, n=4-5 in each group) while the expression of the prosurvival proteins (Bcl2 and caveolin3) was significantly upregulated (p<0.05, n=4-5 (in each group) in post MI. These data indicate that increased SLMAP3 levels serve to protect myocardium post MI through mechanisms which promote cell survival and limit cardiac fibrosis. Strategies to increase SLMAP3 level in myocardium may provide new therapeutic options in the treatment of heart failure.
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Lee, Heow Won. "Role of BDNF in Cardiac Remodeling and Dysfunction in Rats After Myocardial Infarction." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39642.
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Myocardial infarction (MI) induced heart failure (HF) is a leading cause of morbidity and mortality over the world. Regular exercise improves quality of life and decreases hospitalization and mortality of patients with HF. In animals, exercise post MI attenuates progressive cardiac remodeling and cardiac dysfunction, and decreases neuronal activity in the paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM), which are key brain nuclei contributing to sympathetic hyperactivity post MI. The peripheral and central molecular mechanisms underlying these beneficial effects of exercise are not well understood. We studied one possible mechanism, brain-derived neurotrophic factor (BDNF), an exercise-induced factor, which via binding to its receptor tropomyosin-related kinase B (TrkB) may contribute to improvement of cardiac function post MI. In the brain, the ratio between two isoforms of the TrkB receptor, full-length and truncated forms (TrkB.FL/TrkB.T1) determines the extent of intracellular responses to mature BDNF (mBDNF; an active form of BDNF) and a decrease in this ratio may reflect down-regulation of BDNF-TrkB.FL signaling. Ca2+/calmodulin-dependent kinase II (CaMKII) and protein kinase B (Akt) are intracellular factors of BDNF-TrkB signaling in hippocampal/cortical neurons. Activation of cardiac BDNF-TrkB signaling may increase cardiomyocyte survival and myocardial contractility. In hypertensive rats, the role of BDNF-TrkB signaling in the PVN and RVLM appears opposite with activation of this axis in the PVN increasing, but in the RVLM decreasing sympathetic nerve activity (SNA). However, activation of CaMKII and Akt in the PVN and RVLM both mediate increase in SNA. The specific role of BDNF-TrkB signaling in the PVN and RVLM of rats with HF post MI has not yet been studied. We hypothesized that exercise training post MI enhances BDNF-TrkB signaling pathways in the left ventricle (LV) and RVLM, but inhibits in the PVN, and thereby preserves cardiac structure and function post MI. We evaluated changes in BDNF-TrkB axis and intracellular factors CaMKII and Akt in the non-infarct area of the LV, PVN and RVLM in sedentary and exercising rats with MI. The impact of systemic blockade of BDNF-TrkB signaling was assessed with ANA-12, a selective non-competitive antagonist of TrkB receptors. In the infarct area of the LV, mBDNF protein decreased and TrkB.T1 protein increased. In the non-infarct area, mBDNF tended to be decreased without change in TrkB.T1 expression. The activities of CaMKII and Akt were decreased in the non-infarct area of the LV. In the PVN and RVLM, the TrkB.FL/TrkB.T1 ratio was decreased but without changes in mBDNF and downstream factors except for decrease in Akt activity in the RVLM. Exercise training improved ejection fraction (EF), cardiac index and LV end-diastolic pressure, but only the exercise-induced improvement of EF was blocked by ANA-12. In the non-infarct area of the LV, exercise prevented decreases in mBDNF, CaMKII and Akt, and these effects were prevented by ANA-12. In the PVN, exercise increased mBDNF and decreased Akt activity, whereas in the RVLM, exercise had no effect on mBDNF but decreased CaMKII activity. The exercise-induced increase mBDNF in the PVN and decrease in p-CaMKIIβ expression in the RVLM were prevented by ANA-12. Our findings suggest that down-regulation of BDNF-TrkB signaling post MI is prominent in the LV with decreases in mBDNF protein in the infarct area and intracellular factors CaMKII and Akt in the non-infarct area. Increases in mBDNF, CaMKII and Akt in the LV by exercise may contribute to improvement of EF. In the PVN and RVLM, despite a decrease in the ratio of TrkB.FL/TrkB.T1 in both brain nuclei, only Akt activity decreased in the RVLM post MI. Exercise-induced decreases in activities of CaMKII in the RVLM and Akt in the PVN may both contribute to reduction in sympathetic hyperactivity post MI.
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Al-Darraji, Ahmed Hamish Neamah. "AZITHROMYCIN THERAPY REDUCES CARDIAC INFLAMMATION AND MITIGATES ADVERSE CARDIAC REMODELING AFTER MYOCARDIAL INFARCTION." UKnowledge, 2019. https://uknowledge.uky.edu/pharmacol_etds/30.
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Introduction: Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide. Induced by cardiomyocyte death, MI initiates a prolonged and uncontrolled inflammatory response which impairs the healing process. Immune cells, such as macrophages, play a central role in organizing the early post-MI inflammatory response and the subsequent repair phase. Two activation states of macrophages have been identified with distinct and complementary functions (inflammatory vs. reparatory). This bimodal pattern of macrophage activation is an attractive therapeutic target to favorably resolve post-MI inflammation and enhance recovery. It has been demonstrated that azithromycin (AZM), a commonly used antibiotic with immunomodulatory effects, polarizes macrophages towards the reparatory phenotype. AZM has an excellent safety profile and has been approved for human use. We hypothesize that AZM reduces inflammation and improves heart function in MI.
Methods and results: In our initial studies, we demonstrated that oral free AZM (160 mg/kg daily for 7 days), initiated 3 days prior to MI, enhances post-MI cardiac recovery as a result of shifting macrophages to the reparatory state. We observed a significant reduction in mortality with AZM therapy. AZM-treated mice showed a significant decrease in pro-inflammatory and an increase in reparative macrophages, decreasing the pro-inflammatory/reparative macrophage ratio. Macrophage changes were associated with a significant decline in pro- and an increase in anti-inflammatory cytokines. Additionally, AZM treatment was correlated with a distinct decrease in neutrophil count due to apoptosis, a known signal for shifting macrophages towards the reparative phenotype. Finally, AZM treatment improved cardiac recovery, scar size, and angiogenesis. We designed this proof of concept study using pre-MI AZM therapy to achieve steady state levels prior to injury. Therefore, in our follow-up studies we targeted inflammatory macrophages using a non-Pegylated liposomal formulation of AZM (Lazm) which has been shown in multiple studies to promote drug efficacy and minimize off-target effects. To test the hypothesis that Lazm is more effective and safer than free AZM, low doses of free/liposomal AZM (10 or 40 mg/kg, administered intravenously) were initiated immediately after MI. We observed that Lazm induces early resolution of the post-MI inflammatory response as evidenced by switching of the activation state of monocytes/macrophages towards the reparatory phenotype. Neutrophils were substantially decreased, particularly pro-inflammatory neutrophils. Cytokine profiles were also shifted to the anti-inflammatory status with Lazm therapy. Taken together, AZM treatment resulted in a significant shift in macrophage activation towards the reparatory state. The shift in inflammatory state was accompanied by a decrease in apoptosis and infarct size in the injured heart, as well as enhanced angiogenesis and LV functional recovery in our long-term studies. In addition, Lazm was protective against off-target effects of AZM on the heart.
Conclusion: This is the first evidence of a novel and clinically-relevant therapeutic strategy to modulate post-MI inflammation. We found that AZM reduces cardiac inflammation and improves adverse cardiac remodeling after infarction via promoting a shift of macrophage activation state. The overarching significance of this work is the modulation of sterile inflammation, which can be a viable therapeutic target in many conditions including stroke and heart attack. Additionally, this is the first study to demonstrate the immune modulation properties of liposomal AZM, which has wide potential therapeutic applications beyond the cardiovascular field. Importantly, liposomal formulation of AZM is protective from its cardiac off-target effects. Our findings strongly support clinical trials using AZM as a novel and clinically relevant therapeutic target to improve cardiac recovery and reduce heart failure post-MI in humans.
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Nelson, Charles A. L. "Relationship between the transmural distribution of myocardial scar and ventricular function /." [St. Lucia, Qld.], 2004. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18564.pdf.
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Guo, Xiaobing. "Role of angiotensin in sarcoplasmic reticulum remodeling in heart failure due to myocardial infarction." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0022/MQ51720.pdf.
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Luther, Daniel J. "The role of type VI collagen in cardiac remodeling following myocardial infarction in mice." Thesis, Kent State University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3618869.
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Cardiac remodeling is a dynamic process largely propagated by cardiac fibroblasts (CFs), the critical mediators of wound repair. Following myocardial infarction (MI), this process is accelerated resulting in aberrant structural changes to the heart. Investigation into the fibrotic responses of the heart to injury have focused on collagens type I and III however, we have uncovered a novel role for type VI collagen (Col6). Here, we report the effects of the deletion of Col6 from the myocardium during post-MI wound repair and demonstrate that Col6-/- mice are resistant to ischemic injury resulting in reductions in infarct size and preserved cardiac function. To investigate potential mechanisms responsible for the cardioprotection in Col6-/- mice, we used histological approaches to assess the cardiac ECM for structural changes that may alter cardiac wound repair. Our results suggest looser formed collagen fibers and an abundance of type III collagen in the post-MI hearts of Col6-/- mice, in contrast to the abundance of type I collagen observed in WT post-MI mice. Additionally, we hypothesized that altered mitochondrial structure and function in the hearts of Col6 -/- mice also presents a potential mechanism leading to protection from ischemic injury. To test this, we used electron microscopy (EM) and molecular approaches to assess mitochondria of Col6-/- post-MI mice. EMs of Col6-/- uninjured hearts illustrate normal mitochondrial morphology however, at 3 days post-MI Col6-/- mice demonstrate increased mitochondrial fusion, in contrast to increased mitochondrial swelling and fission observed in WT mice. By 14 days, Col6-/- mitochondria appear normal while WT post-MI mice have disrupted mitochondria. Western blot indicated differences in mitochondrial fusion/fission protein flux between groups at 24 hrs. post-MI. Oxygen consumption of isolated mitochondria from Col6-/- sham hearts demonstrate a reduced mitochondrial respiratory control index (RCI) compared to WT controls. Following MI the RCI of Col6-/- mice did not significantly decline, as was observed in WT post-MI mice. Together, these data indicate that Col6-/- mice are protected from ischemic injury leading to improved cardiac remodeling and function following MI, and differences in ECM structure and mitochondrial function are possible mechanism(s) underlying the unexpected cardioprotection observe in Col6 -/- mice.
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Guo, Xiaobing. "Role of angiotensin in sarcoplasmic reticulum remodeling in heart failure due to myocardial infarction." Ottawa : National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.nlc-bnc.ca/obj/s4/f2/dsk1/tape2/PQDD%5F0022/MQ51720.pdf.
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Luther, Daniel J. "The Role of Type VI Collagen In Cardiac Remodeling Following Myocardial Infarction In Mice." Kent State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=kent1376067347.
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Adapala, Ravi kumar. "ROLE OF MECHANOSENSITIVE ION CHANNEL TRPV4 IN CARDIAC REMODELING." Kent State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1520341694907018.
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Elnakish, Mohammad T. "Mechanisms and Functional Consequences of Cardiac Remodeling: Role of Myocardial Rac1 and Vascular Profilin1 Genes." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1363694358.
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Ju, Haisong. "Remodeling and regulation of cardiac collagen during the development of heart failure due to myocardial infarction." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0004/NQ31995.pdf.
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Sharp, III Thomas E. "DRUG AND CELL–BASED THERAPIES TO REDUCE PATHOLOGICAL REMODELING AND CARDIAC DYSFUNCTION AFTER ACUTE MYOCARDIAL INFARCTION." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/445275.
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PhysiologyPh.D.
Remarkable advances have been made in the treatment of cardiovascular diseases (CVD), however, CVD still accounts for the most deaths in industrialized nations. Ischemic heart disease (IHD) can lead to acute coronary syndrome (ACS) (myocardial infarction [MI]). The standard of care is reperfusion therapy followed by pharmacological intervention to attenuate clinical symptoms related to the MI. While survival from MI has dramatically increased with the implementation of reperfusion therapy, these individuals will inevitably suffer progressive pathological remodeling leaving them predispose to develop heart failure (HF). HF is a clinical syndrome defined as the impairment of the heart to maintain organ perfusion at rest and/or during times of exertion (i.e. exercise intolerance). Clinically, this is accompanied by dyspnea, pulmonary or splanchnic congestion and peripheral edema. Physiologically, there is neurohormal activation through the classical β–adrenergic and PKA–dependent signalin
Temple University--Theses
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Wang, Yves Terence. "Effects of Interventions Following Myocardial Infarction: Defibrillation-Induced Electroporation and Reverse Remodeling Following Surgical Ventricular Reconstruction." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1327695637.
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Schneeberger, Dana L. "Biofeedback-Assisted Stress Management Training to Reverse Myocardial Remodeling in Patients with End-Stage Heart Failure." Cleveland State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=csu1338862672.
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Legallois, Damien. "Paramètres biologiques et échocardiographiques et remodelage ventriculaire gauche après syndrome coronarien aigu avec sus-décalage du segment ST Definition of left ventricular remodelling following ST-elevation myocardial infarction: a systematic review of cardiac magnetic resonance studies in the past decade Left atrial strain quantified after myocardial infarction is associated with ventricular remodeling The relationship between circulating biomarkers and left ventricular remodeling after myocardial infarction: an updated review Serum neprilysin levels are associated with myocardial stunning after ST-elevation myocardial infarction Is plasma level of Coenzyme Q10 a predictive marker for left ventricular remodeling after revascularization for ST-segment elevation myocardial infarction ?" Thesis, Normandie, 2020. http://www.theses.fr/2020NORMC429.
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Le remodelage ventriculaire gauche est une complication fréquente des patients ayantprésenté un syndrome coronarien aigu, pouvant conduire à terme à une situation d’insuffisancecardiaque. Il est donc important de connaître les facteurs associés à la survenue d’un remodelageventriculaire afin de dépister plus précocement les patients à plus haut risque d’insuffisance cardiaqueet ainsi optimiser leur prise en charge. Ce travail comprend deux axes. Le premier porte sur larecherche de nouveaux paramètres d’imagerie associés à la survenue du remodelage. Nous avonsdans un premier temps réalisé une revue de la littérature concernant la définition du remodelageventriculaire gauche en imagerie par résonance magnétique. Puis, nous avons conduit deux étudesayant pour but de rechercher une association entre (i) le strain atrial gauche et, (ii) le gradient depression intraventriculaire gauche diastolique, évalués en échocardiographie 24-48 heures après lesyndrome coronarien aigu et le remodelage ventriculaire gauche au cours du suivi. Le second axe portesur les biomarqueurs associés au remodelage ventriculaire post-infarctus. Nous avons réalisé une revuede la littérature au sujet des biomarqueurs qui, dosés lors de l’hospitalisation initiale, sont associés àl’existence d’un remodelage lors du suivi. Nous avons ensuite étudié la valeur prédictrice de deuxbiomarqueurs (la néprilysine et le coenzyme Q10) pour la survenue d’un remodelage ventriculairegaucheLeft ventricular remodeling is a common complication in patients following acutemyocardial infarction and may lead to heart failure. Some baseline parameters are associated withremodeling at follow-up, allowing to better discriminate patients with an increased risk of heart failureto optimize therapeutics. This work has two axes, focused on imaging and biological parametersassociated with left ventricular remodeling, respectively. First, we reviewed past studies that definedremodeling using cardiac magnetic resonance imaging. Then, we studied the association betweensome echocardiographic parameters (left atrial strain and diastolic intraventricular pressure gradient)and left ventricular remodeling after ST-elevation myocardial infarction. In the other axis, wereviewed biomarkers that have been associated with left ventricular remodeling in prior studies. Then,we investigated the association between neprilysin and coenzyme Q10 levels and left ventricularremodeling in STEMI patients
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Foster, Cerrone R., Laura L. Daniel, Christopher R. Daniels, Suman Dalal, Mahipal Singh, and Krishna Singh. "Deficiency of Ataxia Telangiectasia Mutated Kinase Modulates Cardiac Remodeling Following Myocardial Infarction: Involvement in Fibrosis and Apoptosis." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/8570.
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Ataxia telangiectasia mutated kinase (ATM) is a cell cycle checkpoint protein activated in response to DNA damage. We recently reported that ATM plays a protective role in myocardial remodeling following β-adrenergic receptor stimulation. Here we investigated the role of ATM in cardiac remodeling using myocardial infarction (MI) as a model. Methods and Results: Left ventricular (LV) structure, function, apoptosis, fibrosis, and protein levels of apoptosisand fibrosis-related proteins were examined in wild-type (WT) and ATM heterozygous knockout (hKO) mice 7 days post-MI. Infarct sizes were similar in both MI groups. However, infarct thickness was higher in hKO-MI group. Two dimensional M-mode echocardiography revealed decreased percent fractional shortening (%FS) and ejection fraction (EF) in both MI groups when compared to their respective sham groups. However, the decrease in %FS and EF was significantly greater in WT-MI vs hKO-MI. LV end systolic and diastolic diameters were greater in WT-MI vs hKO-MI. Fibrosis, apoptosis, and α-smooth muscle actin staining was significantly higher in hKO-MI vs WT-MI. MMP-2 protein levels and activity were increased to a similar extent in the infarct regions of both groups. MMP-9 protein levels were increased in the non-infarct region of WT-MI vs WT-sham. MMP-9 protein levels and activity were significantly lower in the infarct region of WT vs hKO. TIMP-2 protein levels similarly increased in both MI groups, whereas TIMP-4 protein levels were significantly lower in the infarct region of hKO group. Phosphorylation of p53 protein was higher, while protein levels of manganese superoxide dismutase were significantly lower in the infarct region of hKO vs WT. In vitro, inhibition of ATM using KU-55933 increased oxidative stress and apoptosis in cardiac myocytes.
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Del, Rio Carlos Luis. "Remodeling of Myocardial Passive Electrical Properties: Insights into the Mechanisms of Malignant Arrhythmias and Sudden Cardiac Death." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429553013.
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Kelloniemi, A. (Annina). "Novel factors regulating cardiac remodeling in experimental models of cardiac hypertrophy and failure." Doctoral thesis, Oulun yliopisto, 2018. http://urn.fi/urn:isbn:9789526220291.
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Abstract Cardiac loading induces left ventricular hypertrophy and cardiac remodeling which when prolonged, leads to heart failure, a complex syndrome affecting approximately 1-2% of the adult population of the Western world with a prevalence increasing with age. Pathological remodeling involves functional and structural changes that are associated with fetal gene expression, sarcomeric re-organization, hypertrophy of cardiomyocytes, fibrosis, inflammation, oxidative stress and impairment of metabolism. The aim of this study was to investigate the role of three novel factors during the cardiac remodeling process with different experimental models of cardiac overload. Phosphatase and actin regulator 1 (Phacr1) expression was rapidly downregulated due to myocardial infarction (MI). Adenovirus-mediated Phactr1 overexpression changed the skeletal α-actin to cardiac α-actin ratio in both healthy and infarcted rat hearts and cultured cardiomyocytes. Phactr1 could regulate the actin isoform switch via the serum response factor (SRF). The expression of transforming growth factor (TGF)- β-stimulated clone 22 (TSC-22) was rapidly induced by multiple hypertrophic stimuli and was also evident post-MI. In addition, TSC-22 could regulate collagen 3a1 expression in the heart. The expression of retinal degeneration 3-like (Rd3l) was downregulated in response to pressure overload and also downregulated post-MI. Rd3l knockout mice expressed increased myocyte hypertrophy and cardiac dysfunction in response to a transverse aortic constriction (TAC) induced pressure overload. This thesis provides novel information about Phactr1, TSC-22 and Rd3l in load-induced cardiac hypertrophy and remodeling. Collectively these studies increase our understanding of the regulatory mechanisms underlying the progression of heart failureTiivistelmä Sydämen kuormitus saa aikaan vasemman kammion liikakasvun eli hypertrofian ja sydämen uudelleenmuovautumisen, mikä pitkittyessään johtaa sydämen vajaatoimintaan. Sydämen vajaatoiminta on monimutkainen oireyhtymä, josta länsimaissa kärsii noin 1-2 % aikuisväestöstä, ja esiintyvyys nousee iän myötä. Patologisessa uudelleenmuovautumisessa tapahtuu toiminnallisia ja rakenteellisia muutoksia, joihin liittyy muutoksia geenien ilmentymisessä, sarkomeerin uudelleen järjestäytymistä, sydänlihassolujen koon kasvua, fibroosia, tulehdusta, oksidatiivista stressiä ja aineenvaihdunnan huonontumista. Tämän työn tarkoituksena oli tutkia kolmen uuden tekijän roolia sydämen uudelleenmuovautumisessa erilaisissa kokeellisissa sydämen kuormituksen malleissa. Fosfataasin ja aktiinin säätelijä 1:n (Phactr1) ilmentyminen väheni nopeasti infarktin seurauksena. Adenovirusvälitteinen Phactr1:n ylituotanto muutti luusto- ja sydänlihasaktiinien isomuotojen suhdetta sekä terveessä että infarktisydämessä, samoin viljellyissä sydänlihassoluissa. Phactr1 saattaa säädellä isomuotojen suhdetta seerumiresponsiivisen tekijän (SRF) avulla. Transformoituvan kasvutekijä β1:n stimuloima proteiini 22:n (TSC-22) ilmentyminen nousi nopeasti usean hypertrofisen stimuluksen seurauksena sekä infarktin jälkeen. Lisäksi TSC-22 voisi säädellä kollageeni 3a1:n ilmentymistä sydämessä. Retinan degeneroituvan proteiinin 3 kaltaisen tekijän (Rd3l) ilmentyminen väheni sekä painekuormituksen että infarktin seurauksena. Rd3l-poistogeenisillä hiirillä aortan ahtauman aiheuttama painekuormitus sai aikaan lisääntynyttä sydänlihassolujen hypertrofiaa ja sydämen toimintahäiriöitä. Tämä väitöskirjatutkimus tuo uutta tietoa Phactr1-, TSC-22- ja Rd3l-geeneistä kuormituksen aiheuttamassa sydämen hypertrofiassa ja uudelleenmuovautumisessa. Nämä tulokset auttavat osaltaan ymmärtämään monimutkaisia molekyylitason mekanismeja, jotka johtavat sydämen vaajatoiminnan kehittymiseen
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Kruschandl, Katrin. "Einfluss des Z-Scheiben-Proteins Calsarcin-1 auf das Remodeling nach Myokardinfarkt." Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-161653.
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Ziel dieser Arbeit war, in einem experimentellen Ansatz der Frage nachzugehen, welche pathophysiologischen Veränderungen in Bezug auf Hypertrophie und Funktionalität der Herzmuskulatur nach einem Myokardinfarkt durch Calsarcin-1 hervorgerufen werden und welchen Einfluss das Z-Scheiben-Protein in-vivo auf den Kalzium-Calmodulin Signalweg besitzt. Für die dafür durchgeführten Untersuchungen konnte auf drei verschiedene Mauslinien zurückgegriffen werden (Calsarcin-1 knockout-Mäuse, Calsarcin-1 transgene Mäuse, Wildtypmäuse). Die vorliegende Arbeit baut auf den in-vitro Ergebnissen von Frey et al. (2004) auf. Insgesamt wurden 278 Mäuse einer Infarkt- oder Scheinoperation unterzogen. Fünf Wochen nach ihrer Operation wurde das Herz jeder Maus mittels Ultraschall vermessen und auf seine Funktionstüchtigkeit untersucht. Anschließend wurden die Tiere getötet. Die entnommenen Herzen wurden gewogen, die entnommenen Unterschenkel vermessen. Insgesamt 60 Herzen wurden nach konventionellen histologischen Verfahren HE-gefärbt. 39 Mäuse wurden 24 Stunden nach ihrer Infarktoperation getötet. Ihre Herzen wurden mit Evans-blue und Tetrazoliumchlorid gefärbt. Insgesamt gingen Gewebeproben von 67 Herzen in die Untersuchungen auf RNA-Ebene (Real-Time PCR, Dot Blot) ein. Die Herzen von 40 Tieren konnten auf Proteinebene (Western Blot) untersucht werden. Die echokardiologische Untersuchung der Mäuse nach fünf Wochen zeigte eine deutliche Dilatation des linken Ventrikels derjenigen Tiere, die einer Infarktoperation unterzogen worden waren. Die größte Dilatation der drei Infarktgruppen wiesen die Mäuse auf, die nicht in der Lage sind, das Z-Scheiben-Protein Calsarcin-1 auszubilden (0,558 cm (ko Mi) vs. 0,494 cm (Wt Mi); p < 0,001). Diese Mäuse zeigten auch gegenüber den anderen beiden Infarktgruppen die ausgeprägteste systolische Dysfunktion (FS von 0,238% (ko Mi) vs. 0,376% (Wt Mi) und 0,353% (tg Mi); jeweils p < 0,001). Keine Unterschiede bestanden zwischen den Gruppen der scheinoperierten Mäuse. Morphometrische Analysen belegten eine deutliche Hypertrophie der Calsarcin-1 defizienten Mäuse, die durch die Infarktoperation einer biomechanischen Stresssituation ausgesetzt wurden. Als Hypertrophiemaß wurde der Quotient aus Herz- und Körpergewicht gewählt, zusätzlich wurde der Quotient aus Herzgewicht und Tibialänge bestimmt. Bei beiden Messungen unterschied sich das Herzgewicht der knockout-Mäuse mit Infarkt signifikant von den anderen beiden Infarktgruppen. Für das Verhältnis von Herz- zu Körpergewicht wurde für die drei Mäusegruppen ermittelt: 7,55 ± 0,6mg/g (ko Mi ), 5,56 ± 0,23mg/g (WtMi) und 5,73 ± 0,4mg/g (tgMi), wobei p < 0,01 bei ko Mi/Wt Mi und p < 0,86 bei tg Mi / Wt Mi. Für das Verhältnis von Herzgewicht zu Tibialänge ergab sich: 12,4mg/mm (ko Mi), 10,11mg/mm (Wt Mi) und 10,02mg/mm (tg Mi) (p < 0,001 koMi / WtMi, p < 0,27 tg Mi / WtMi). Zwischen den Gruppen der scheinoperierten Mäuse wurden keine signifikanten Unterschiede festgestellt. Auch auf zellulärer Ebene wiesen die Calsarcin-1 knockout-Mäuse mit Myokardinfarkt eine deutliche Hypertrophie auf verglichen mit den Wildtyp-Mäusen mit Infarkt und den Calsarcin-1 transgenen Tieren (Zellgrößenzunahme um 43,12% (koMi), 34,85% (WtMi) und 29,12% (tgMi); jeweils p < 0,001). Von allen drei Infarktgruppen zeigten die knockout-Mäuse nach fünf Wochen die ausgeprägteste Narbenbildung (Fläche der Infarktnarbe in % der Fläche des linken Ventrikels: 73,41±7,85% (ko-Mi), 53,71±3,81% (WtMi) und 48,60±6,04% (tgMi)). Übereinstimmend dazu wiesen die knockout-Mäuse mit Myokardinfarkt eine übermäßige Steigerung der ANP Produktion auf mRNA-Ebene auf. Auf Proteinebene konnte eine Steigerung der Produktion von MCIP nachgewiesen werden (ko Mi 4,3 ± 0,5 vs. Wt Mi 2,3 ± 0,3 ; p < 0,01). Zusammenfassend lassen die Ergebnisse auf eine gesteigerte Aktivität von Calcineurin und auf ein pathologisches Remodeling in der Abwesenheit von Calsarcin-1 schließen. Die Überexpression von Calsarcin-1 scheint dagegen eine pathologische Hypertrophie des Herzmuskels abmildern zu können.
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Rabald, Steffen. "Entwicklung der Kontrastmittelechokardiografie am Rattenmodel zur Untersuchung des Einflusses von mesenchymalen Vorläuferzellen auf das Remodeling nach experimentellem Herzinfarkt." Doctoral thesis, Universitätsbibliothek Leipzig, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-66770.
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Es werden in einer kumulativen Dissertationsschrift zwei wissenschaftliche Arbeiten zusammengefasst.
Die erste Arbeit beschreibt die Etablierung der Kontrastmittelechokardiografie zur Charakterisierung des Herzinfarktmodells an der Ratte im zeitlichen Verlauf. Es wird der Ablauf der geometrischen Änderungen am linken Herz nach Herzinfarkt gezeigt. Zusätzlich wird die Methode mit anderen etablierten echokardiografischen Methoden verglichen. Hier wird die Messung der linksventrikulären Querschnittsfläche der Volumenbestimmung nach der modifizierten Simpson-Methode gegenübergestellt. Es wird gezeigt, dass die Flächenmessungen, bei Nichtverfügbarkeit der Kontrastmittelechokardiografie eine valide Methode zur Verlaufsbeobachtung im Modell darstellt.
Die zweite Arbeit untersucht im Rattenversuch den Einfluss von mesenchymalen Vorläuferzellen aus Nabelschnurblut auf die Entwicklung des Herzversagens nach Herzinfarkt. Die Injektion der Zellen erfolgt direkt in das Herzmuskelgewebe am Rand des Infarktareals. Zusätzlich zur Phänotypisierung mittels Echokardiografie wurden hämodynamische Messungen, sowie immunhistochemische und molekularbiologische Untersuchungen vorgenommen. Es konnte in einem Multigruppendesign gezeigt werden, dass im vorliegenden Versuch durch die Injektion von Vorläuferzellen kein Einfluss auf die geometrischen und biomechanischen Änderungen nach Herzinfarkt genommen werden konnte. Es konnten jedoch zusätzlich Differenzen zwischen den Versuchsgruppen in der Genexpression von Signalmolekülen der extrazellulären Matrix gezeigt werden, welche Spekulationen über den Einfluss der Zellen auf parakrine Mechanismen im Herzgewebe zulassen.
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Fan, Zhaobo. "Control of Cardiac Extracellular Matrix Degradation and Cardiac Fibrosis after Myocardial Infarction." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1480662216531284.
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Naugle, Jennifer Elaine. "Regulation of cardiac fibroblast function via cyclic AMP, collagen I, III, and VI implications for post-myocardial infarction remodeling /." Kent State University / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=kent1152897621.
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Foster, Cerrone R., Mahipal Singh, Venkateswaran Subramanian, and Krishna Singh. "Ataxia Telangiectasia Mutated Kinase Plays a Protective Role in β-Adrenergic Receptor-Stimulated Cardiac Myocyte Apoptosis and Myocardial Remodeling." Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etsu-works/8574.
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β-Adrenergic receptor (β-AR) stimulation induces cardiac myocyte apoptosis and plays an important role in myocardial remodeling. Here we investigated expression of various apoptosis-related genes affected by β-AR stimulation, and examined first time the role of ataxia telangiectasia mutated kinase (ATM) in cardiac myocyte apoptosis and myocardial remodeling following β-AR stimulation. cDNA array analysis of 96 apoptosis-related genes indicated that β-AR stimulation increases expression of ATM in the heart. In vitro, RT-PCR confirmed increased ATM expression in adult cardiac myocytes in response to β-AR stimulation. Analysis of left ventricular structural and functional remodeling of the heart in wild-type (WT) and ATM heterozygous knockout mice (hKO) 28 days after ISO-infusion showed increased heart weight to body weight ratio in both groups. M-mode echocardiography showed increased percent fractional shortening (%FS) and ejection fraction (EF%) in both groups 28 days post ISO-infusion. Interestingly, the increase in %FS and EF% was significantly lower in the hKO-ISO group. Cardiac fibrosis and myocyte apoptosis were higher in hKO mice at baseline and ISO-infusion increased fibrosis and apoptosis to a greater extent in hKO-ISO hearts. ISO-infusion increased phosphorylation of p53 (Serine-15) and expression of p53 and Bax to a similar extent in both groups. hKO-Sham and hKO-ISO hearts exhibited reduced intact β1 integrin levels. MMP-2 protein levels were significantly higher, while TIMP-2 protein levels were lower in hKO-ISO hearts. MMP-9 protein levels were increased in WT-ISO, not in hKO hearts. In conclusion, ATM plays a protective role in cardiac remodeling in response to β-AR stimulation.
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James, Caytlin, Suman Dalal, Mahipal Singh, and Krishna Singh. "Lack of Osteopontin Decreases Systolic and Diastolic Functional Parameters of the Heart Following Myocardial Ischemia/Reperfusion Injury." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/104.
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Ischemic heart disease represents a leading cause of death worldwide. Ischemia denotes an insufficient supply of oxygenated blood to the heart due to occlusion of the coronary vessels. Timely reperfusion, i.e., restoring blood flow to the ischemic part of the heart, limits ischemic damage. However, reperfusion itself induces injury to the heart. This phenomenon is referred as ischemia/reperfusion (I/R) injury. Osteopontin (OPN), also known as cytokine Eta-1, is a cell-secreted extracellular matrix protein. Expression of OPN increases in the heart in response to a variety of pathological conditions. Mice lacking OPN exhibit exaggerated left ventricular dilation in non-reperfused model of myocardial remodeling. Cardioprotective role of OPN has also been demonstrated in a mouse model of repetitive I/R injury for 7 days. The objective of this study was to examine the role of OPN in modulation of systolic and diastolic parameters of the heart following I/R injury in a time-dependent manner. For this study, wild type (WT) and OPN knockout (KO) mice aged ~4 months were subjected to cardiac ischemia by the ligation of left anterior descending coronary artery (LAD). Following 45 min of ischemia, the LAD was reperfused by snipping the ligature. Heart function was measured using echocardiography at baseline, 3, 7, 14, and 27 days following I/R injury. M-mode echocardiographic images were used to calculate the systolic parameters (% fractional shortening [%FS], % ejection fraction [%EF], and end-systolic volume [ESV]), while pulse wave Doppler images were used to calculate diastolic parameter (aortic ejection time; [AET]). Global cardiac function was evaluated using myocardial performance index (MPI; a Doppler-derived index which combines systolic and diastolic functions). At basal levels, most of the systolic and diastolic parameters remained unchanged between the two groups. I/R injury decreased %FS and EF in both groups vs the baseline values at 3, 7, 14 and 27 days post-I/R. However, the decrease in %FS and EF was significantly greater in KO-I/R vs WT-I/R group. ESV was significantly higher in WT mice 7 days post-I/R, and stayed higher 14 and 27 days post-I/R vs baseline. However, the increase in ESV was significantly greater in KO mice 3 day post-I/R, and remained higher vs WT-I/R during the time course. AET was lower in WT group 14 days post-I/R vs baseline. On the other hand, AET was significantly lower in KO group 3, 7, 14 and 27 days post-I/R vs WT-I/R. MPI was higher in WT group 7 days post-IR vs baseline. MPI decreased significantly in WT group 27 days vs 7 days post-I/R. In KO group, MPI was significantly higher than WT mice at baseline, and remained higher 3 and 27 day post-I/R vs WT-I/R. Thus, lack of OPN decreases systolic and diastolic functional parameters of the heart following I/R injury, suggesting a cardioprotective role of OPN in myocardial remodeling post-IR.
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James, Caytlin. "Lack of Osteopontin Induces Systolic and Diastolic Dysfunction in the Heart Following Myocardial Ischemia/Reperfusion Injury." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/honors/528.
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Ischemic heart disease is a leading cause of death worldwide. Osteopontin (OPN), a cell-secreted extracellular matrix protein, is suggested to play a cardioprotective role in mouse models of ischemic heart disease. The objective of this study was to examine the role of OPN in modulation of systolic and diastolic functional parameters of the heart following mouse ischemia/reperfusion (I/R) injury. For this, wild-type (WT) and OPN-knockout (KO) mice aged approximately 4 months were subjected to cardiac ischemia for 45 minutes by the ligation of the left anterior descending coronary artery (LAD) followed by reperfusion of LAD by snipping the ligature. Heart function was measured using echocardiography at baseline, 1, 3, 7, 14, and 27 days post-I/R injury. M-mode echocardiographic images were used to calculate % fractional shortening [%FS], % ejection fraction [%EF], end-systolic volume [ESV], and end-diastolic volume [EDV], while pulsed wave Doppler images were used to measure aortic ejection time [AET], isovolumic relaxation time [IVRT], and total systolic time [TST]. Velocity of circumferential fiber shortening (Vcf) was calculated using FS and AET. I/R injury significantly decreased %EF and %FS in both WT and KO groups at all time points (1, 3, 7, 14, and 27 days post-I/R) versus the baseline. However, the decrease in % EF and %FS was significantly greater in KO-I/R group versus WT-I/R at 3, 7, 14 and 27 days post-I/R. I/R-mediated increase in ESV and EDV were significantly greater in KO-MI group versus WT-MI 3 day post-I/R. AET was significantly higher in WT-I/R group 27 days post-I/R versus baseline. However, AET was significantly lower in KO-I/R group 3 and 27 days post-I/R versus WT-I/R. IVRT was significantly higher in KO-I/R group 27 days post-I/R vs baseline. However, IVRT was significantly lower in KO-I/R group 1 day post-I/R vs WT-I/R. TST remained unchanged in WT and KO groups post-I/R versus their respective baseline groups. However, TST was significantly lower in KO-I/R group versus WT-I/R at 3 days post-I/R. Vcf was significantly higher at basal levels in the KO versus WT mice. I/R injury decreased Vcf in both groups versus their baseline at all time-points. These data provide evidence that lack of OPN deteriorates systolic and diastolic functional parameters of the heart following I/R injury, suggesting a cardioprotective role of OPN in myocardial remodeling post-IR.
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Rosano, Jenna Marie. "Engineering Nanoparticles for Targeted Delivery of Growth Factors to Prevent Cardiac Remodeling After an MI." Master's thesis, Temple University Libraries, 2010. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/82332.
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Mechanical EngineeringM.S.E.
Myocardial infarction (MI) is a leading cause of death in the United States, claiming the lives of approximately 500,000 people each year. The infarcted heart undergoes a compensatory process called cardiac remodeling, which adversely changes left ventricular (LV) size and function and eventually may lead to heart failure. To date, the only clinical treatments for this condition include surgical restoration of blood flow to the ischemic region (e.g., angioplasty), or pharmacological treatments (e.g., angiotensin converting enzyme inhibitors) which indirectly manage the symptoms of cardiac remodeling. Reperfusion of ischemic heart tissue significantly limits myocardial damage after an MI; however, many MI patients are not candidates for traditional reperfusion surgery. Recently, there has been much interest in non-surgical myocardial reperfusion via pro-angiogenic compounds, specifically vascular endothelial growth factor (VEGF). Although animal studies using therapeutic VEGF have shown promising results, these results have failed to translate into successful clinical trials. This may be due to the short half-life of VEGF in circulation. Increasing the dose of VEGF may increase its availability to the target tissue, but harmful side-effects remain a concert. Encapsulating VEGF and selectively targeting it to the MI border zone may improve vascularization, cardiac function, reduce adverse remodeling associated with MI, and may avoid harmful side effects associated with systemic delivery. Anti-P-selectin conjugated immunoliposomes containing VEGF were developed to target the P-selectin ligand overexpressed in the infarct border zone in a rat MI model. Serial echocardiography and Doppler imaging were used to characterize evolutionary changes in LV geometry and function over a period of four weeks after MI. At four weeks, hearts were excised and stained to measure vascularization and collagen deposition. Targeted VEGF treatment resulted in significant improvements in fractional shortening at four weeks post-infarction (32.9 ± 2.2% for targeted VEGF treated vs. 16.9 ± 1.4% for untreated MI). Functional improvements in treated MI hearts were accompanied by a 74% increase in perfused vessels in the MI border zone, compared to untreated MI hearts. Left ventricular filling dynamics were significantly improved in the targeted VEGF treated group, which resulted in a decrease in LV end diastolic pressure in VEGF treated hearts (23.4 ± 2.9 mm Hg), compared to untreated MIs (81.8 ± 31.8 mm Hg). At four weeks after infarction, hearts treated with targeted VEGF therapy exhibited a 37% reduction in collagen deposition, compared to untreated MI hearts. Targeted VEGF therapy significantly improves vascularization, cardiac function, and moderates adverse cardiac remodeling after an infarction.
Temple University--Theses
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Mojsejenko, Dimitri. "ESTIMATING PASSIVE MATERIAL PROPERTIES AND FIBER ORIENTATION IN A MYOCARDIAL INFARCTION THROUGH AN OPTIMIZATION SCHEME USING MRI AND FE SIMULATION." UKnowledge, 2014. http://uknowledge.uky.edu/me_etds/41.
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Myocardial infarctions induce a maladaptive ventricular remodeling process that independently contributes to heart failure. In order to develop effective treatments, it is necessary to understand the way and extent to which the heart undergoes remodeling over the course of healing. There have been few studies to produce any data on the in-vivo material properties of infarcts, and much less on the properties over the time course of healing. In this paper, the in-vivo passive material properties of an infarcted porcine model were estimated through a combined use of magnetic resonance imaging, catheterization, finite element modeling, and a genetic algorithm optimization scheme. The collagen fiber orientation at the epicardial and endocardial surfaces of the infarct were included in the optimization. Data from porcine hearts (N=6) were taken at various time points after infarction, specifically 1 week, 4 weeks, and 8 weeks post-MI. The optimized results shared similarities with previous studies. In particular, the infarcted region was shown to dramatically increase in stiffness at 1 week post-MI. There was also evidence of a subsequent softening of the infarcted region at later time points post infarction. Fiber orientation results varied greatly but showed a shift toward a more circumferential orientation.
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Kujanpää, K. (Kirsi). "Mechanisms behind stem cell therapy in acute myocardial infarction." Doctoral thesis, Oulun yliopisto, 2016. http://urn.fi/urn:isbn:9789526212920.
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Abstract Ischemic heart disease is one of the leading cause of death in the Western world. There is convincing evidence that stem cell therapy improves cardiac function and reduces the scar formation following an acute myocardial infarction (AMI). The mechanisms involved in the recovery remain partly unknown. Direct injection of stem cells into myocardium is a widely used transplantation technique though there are few details available about the behavior of cells after transplantation. A cardiac explant culture model simulating tissue stress was developed in this study to examine in detail the properties of the stem cells after their transplantation. The migration range in myocardium and the number of adherent stem cells increased with time. In vitro and in vivo studies revealed that after their administration, the stem cells became localized in the slit-like spaces, such as in the capillaries. Even though the study outcomes regarding the impact of stem cell therapy in recovery after AMI have been largely promising, the results of the clinical studies have proved to be more controversial. If one wishes to evaluate the true contribution of the stem cell therapy to the recovery, it is essential to devise a reliable study method for cell targeting. Here, iron labeled stem cells in combination with magnetic resonance imaging (MRI) were used. The MRI data corresponded to the histological results. Thus, it is concluded that MRI is a feasible method for monitoring the effectiveness of cell targeting. Stem cell treatment was shown to increase cardiac function at three weeks after AMI. If there was a high number of stem cells in cardiac tissue after transplantation, this predicted a greater improvement in cardiac function. Improper stem cell injection may lead to leakage of the stem cells out of the myocardium, leading to unreproducible study results. Inflammation modulating factors secreted by the stem cells are considered as key mechanisms in the recovery after AMI. There were differences in the cytokine levels between the stem cell treated and control groups in a clinical and in vivo animal study i.e. stem cell therapy exerted a balancing effect on the inflammatory process, a crucial component in the optimal recovery after AMI. The present study reveals many properties of stem cells, importance of cell targeting and the influence of stem cell therapy on cytokine levels after AMITiivistelmä Iskeeminen sydänsairaus on yksi yleisimmistä kuolinsyistä länsimaissa. Tutkimusten mukaan kantasoluterapia parantaa sydämen toimintakykyä ja pienentää akuutin sydäninfarktin jälkeen sydämeen muodostuvan arpikudoksen määrää. Paranemiseen liittyvät mekanismit ovat edelleen osittain tuntemattomia. Kantasolujen ruiskutus suoraan sydämeen on paljon käytetty menetelmä, vaikka solujen käyttäytymistä ei tunneta tarkkaan.Tutkimuksessa kehitetyn kudoksen stressitilaa simuloivan sydänkudoksen kasvatusmenetelmän avulla tutkittiin siirrettyjen kantasolujen toimintaa yksityiskohtaisesti. Kantasolujen vaeltaman matkan sydänkudoksessa ja kiinnittyneiden kantasolujen lukumäärä havaittiin kasvavan ajan kuluessa. In vitro ja in vivo tutkimuksissa havaittiin kantasolujen sijaitsevan ruiskutuksen jälkeen rakomaisissa paikoissa kuten pienissä verisuonissa. Vaikka tutkimustulokset kantasoluterapian hyödyistä paranemisen suhteen ovat pääosin lupaavia, kliinisten tutkimusten tulokset ovat ristiriitaisia. Todellisen kantasoluhoidon vaikutuksen arvioimiseksi tarvitaan luotettava menetelmä varmistamaan kantasolujen hakeutuminen vaurioalueelle. Tässä tutkimuksessa rautaleimattujen kantasolujen paikantamisessa käytetty magneettikuvantaminen vastasi histologisia löydöksiä. Magneettikuvantaminen todettiin käyttökelpoiseksi menetelmäksi solujen paikallistamisessa. Kantasoluhoidon osoitettiin parantavan sydämen toimintakykyä kolme viikkoa akuutin sydäninfarktin jälkeen. Suuri kantasolumäärä sydänkudoksessa siirron jälkeen ennusti parempaa toipumista. Puutteellisesti suoritettu kantasoluruiskutus voi johtaa kantasolujen vuotamiseen pois sydänkudoksesta aiheuttaen vaihtelevuutta tutkimustuloksiin. Kantasolujen erittämiä tulehdusta sääteleviä tekijöitä pidetään tärkeimpänä mekanismina paranemisprosessissa. Tutkimus osoitti eroavaisuuksia kantasoluhoidetun ja kontrolliryhmän välillä. Kliinisessä ja koe-eläintutkimuksessa kantasolusiirrolla todettiin tulehdusreaktiota tasapainottava vaikutus, mikä on tärkeää optimaalisen sydänlihaskudoksen paranemisen kannalta akuutin sydäninfarktin jälkeen. Tutkimus toi esiin monia kantasolujen ominaisuuksia, solujen paikantamisen tärkeyden ja kantasoluhoidon vaikutuksen sytokiinipitoisuuksiin akuutin sydäninfarktin jälkeen
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Daniel, Laura L., Christopher R. Daniels, Saghar Harirforoosh, Cerrone R. Foster, Mahipal Singh, and Krishna Singh. "Deficiency of Ataxia Telangiectasia Mutated Kinase Delays Inflammatory Response in the Heart Following Myocardial Infarction." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/8569.
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Background: Ataxia-telangiectasia results from mutations in ataxia telangiectasia mutated kinase (ATM) gene. We recently reported that ATM deficiency attenuates left ventricular (LV) dysfunction and dilatation 7 days after myocardial infarction (MI) with increased apoptosis and fibrosis. Here we investigated the role of ATM in the induction of inflammatory response, and activation of survival signaling molecules in the heart acute post-MI.
Methods and Results: LV structure, function, inflammatory response, and biochemical parameters were measured in wild-type (WT) and ATM heterozygous knockout (hKO) mice 1 and 3 days post-MI. ATM deficiency had no effect on infarct size. MI-induced decline in heart function, as measured by changes in percent fractional shortening, ejection fraction and LV end systolic and diastolic volumes, was lower in hKO-MI versus WT-MI (n=10 to 12). The number of neutrophils and macrophages was significantly lower in the infarct LV region of hKO versus WT 1 day post-MI. Fibrosis and expression of a-smooth muscle actin (myofibroblast marker) were higher in hKO-MI, while active TGF-β1 levels were higher in the WT-MI 3 days post-MI. Myocyte cross-sectional area was higher in hKO-sham with no difference between the two MI groups. MMP-9 protein levels were similarly increased in the infarct LV region of both MI groups. Apoptosis was significantly higher in the infarct LV region of hKO at both time points. Akt activation was lower, while Bax expression was higher in hKO-MI infarct.
Conclusion: ATM deficiency results in decreased dilative remodeling and delays inflammatory response acute post-MI. However, it associates with increased fibrosis and apoptosis.
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Yang, Yidong. "Using magnetic resonance imaging to track inflammatory cells in a murine myocardial infarction model." Thesis, Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/33883.
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In cellular MRI, micrometer-sized iron oxide particles (MPIO) are a more sensitive contrast agent for tracking inflammatory-cell migration compared to ultra-small superparamagnetic iron oxide particles (USPIO). Inflammation, which promotes adverse tissue remodeling, is known to occur in the viable myocardium adjacent to the necrosed area after a myocardial infarction (MI). This study investigated the temporal relationship between inflammatory cell infiltration and cardiac function during tissue remodeling post-MI using MPIO-enhanced MRI. The MPIO were injected into 7 C57Bl/6 mice (MI+MPIO group) via intravenous administration. The MI was induced 7 days post-MPIO injection. As control groups, 7 mice (Sham+MPIO group) underwent sham-operated surgery without myocardial injury post-MPIO injection and another 6 mice (MI-MPIO group) underwent MI surgery without MPIO injection. MRIs performed post-MI showed a significant signal attenuation at the MI zone in the MI+MPIO group compared to the control groups. The findings suggested that the inflammatory cells containing MPIO infiltrated into the myocardial injury site. Cardiac function was also measured and correlated with the labeled-cell infiltration at the MI site. This study demonstrated a noninvasive technique for monitoring inflammatory cell migration using the MPIO contrast agent. This MPIO-enhanced MRI technique could provide additional insight concerning cardiac disease progression that would improve therapeutic treatment for MI patients.
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Daniel, Laura L. "Role of Ataxia Telangiectasia Mutated Kinase in the Healing Process of the Heart Following Myocardial Infarction." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etd/2504.
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Ataxia telangiectasia (AT), caused by mutations in the gene encoding ataxia telangiectasia mutated kinase (ATM), is a rare autosomal recessive disorder. AT individuals exhibit neuronal degeneration and are predisposed to cancer. Carriers of this disorder are predisposed to cancer and ischemic heart disease. Heart disease, mostly due to myocardial infarction (MI), is a leading cause of death in the US. Following MI, release of catecholamines in the heart stimulates β- adrenergic receptors (β-AR). Our lab has shown that β-AR stimulation increases ATM expression in the heart and myocytes, and ATM plays an important role in β-AR-stimulated myocardial remodeling with effects on function, fibrosis and apoptosis. Using wild-type (WT) and ATM heterozygous knockout (hKO) mice, this study investigated the role of ATM in the inflammatory, proliferative and maturation phases of infarct healing post-MI. During the inflammatory phase, 1 and 3 days post-MI, a deficiency of ATM resulted in decreased left ventricular dilation as measured by echocardiography. It decreased the number of neutrophils and macrophages in the heart 1 day post-MI. Myocardial fibrosis, expression of alpha-smooth muscle actin (α-sma) and apoptosis were higher in the infarct region of ATM deficient hearts. Akt activation (anti-apoptotic) was lower, while Bax expression (pro-apoptotic) was higher in the infarct region of ATM deficient hearts. During the proliferative phase, 7 days post-MI, ATM deficiency attenuated cardiac dysfunction as measured by echocardiography. ATM deficient hearts exhibited increased fibrosis and expression of α-sma in the infarct region with increased myocyte apoptosis in the border area. During the maturation phase, 14 and 28 days post-MI, ATM deficiency resulted in exaggerated cardiac function. It associated with increased fibrosis, expression of α-sma and decreased cardiac cell apoptosis in the infarct region 28 days post-MI. Myocyte hypertrophy was greater in the non-infarct region during ATM deficiency. ATM deficiency decreased expression of p16 (marker of cell senescence) and activation of proapoptotic protein, GSK-3β. Thus, ATM modulates the remodeling processes of the heart including function, fibrosis, apoptosis and hypertrophy post-MI. ATM (1) delays the inflammatory response post-MI, (2) decreases dilative remodeling during inflammatory and proliferative phases and (3) exaggerates dysfunction during the maturation phase.
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Ahmadi, Ali. "Application of Collagen Matrices for Enhancing Cardiac Regeneration." Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31342.
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Injectable biomaterials have emerged as a treatment for myocardial infarction (MI). They can be applied either as an enhancement for cell therapy or as a stand-alone treatment for MI. The main focus of this study was to apply circulating angiogenic cells (CACs) with or without an injectable collagen matrix for MI treatment in a mouse model. Furthermore, a collagen-chitosan matrix was tested for modulating the myocardial maladaptive remodeling post-MI. First, the in vivo thermo-gelling and retention properties of the collagen matrix were validated using positron emission tomography (PET) tracer and quantum dot (Qdot) labelled matrix in MI mouse hearts. The therapeutic potential of the matrix ± CACs was then tested in a mouse MI model. The results showed that CACs-only and matrix-only treatments were associated with cardiac function preservation. However, in combination, CAC + matrix therapy had a synergistic effect and significantly improved cardiac function (echocardiography), perfusion and viability (PET scan), increased cell engraftment and arteriole density, and reduced the infarct size. CAC-matrix interaction through the integrin alpha2 receptor was essential for the observed therapeutic effect. In a third study, the addition of chitosan (a polysaccharide) to the collagen matrix was shown to reduce maladaptive remodeling post-MI by limiting cardiac fibroblast-to-myofibroblast differentiation and scar formation. In conclusion, these collagen-based hydrogels hold promise to enhance cardiac repair as a delivery scaffold for therapeutic cells, and/or as a stand-alone treatment, which can actively modulate the environment including the fibrotic process after MI.
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Al-Shudiefat, Abd Al-Rahman. "Protective role of olive oil and its major component oleic acid in TNF-α induced remodeling subsequent to myocardial infarction in rats." Springer, 2013. http://hdl.handle.net/1993/20074.
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Oxidative stress and inflammation are important factors involved in the progression of heart failure. An important cytokine produced during myocardial infarction (MI) is tumor necrosis factor alpha (TNF-α). TNF-α may induce oxidative stress, cell damage, apoptosis and cardiac dysfunction. Considering the anti-inflammatory and anti-oxidant properties of extra-virgin olive oil and its major component (80%) oleic acid (OA), and their benefits to the cardiovascular system, we hypothesized that the negative effects of TNF-α in the pathogenesis of heart failure will be mitigated by olive oil consumption. This hypothesis was tested by examining the effects of a special diet supplemented with 10% olive oil, in coronary artery ligated animal model of MI. Corn oil (10%) supplementation was used as a control for matching caloric intake. Animals in the sham and ligated groups fed regular chow, olive oil, and corn oil were studied at 4 and 16 weeks post myocardial infarction (PMI).
Mortality, diet consumption, weight gain and conduction system abnormalities were comparable among all ligated groups. Echocardiography showed that MI deteriorated cardiac function, and olive oil restored the function. At 16 weeks PMI, only corn oil fed groups showed significant increase in both total cholesterol and HDL. Corn oil was not able to offer protection to the heart, suggesting that the beneficial effects of olive oil are not due to increased caloric intake or increased HDL. MI increased myocardial TNF-α, oxidative stress, lipid peroxidation, pro-apoptotic protein expression (Bax, cleaved Caspase 3, cleaved PARP, TGFβ, Bnip3), cytochrome C release, MAP kinase activation (p38, JNK) and decreased anti-apoptotic protein Bcl-xL expression at both 4 and 16 weeks PMI, and these changes were modulated by olive oil.
In order to further test the central role of TNF-α PMI, we examined the possible miti-gation of TNF-α induced changes by OA in isolated adult rat cardiomyocytes. TNF-α in-creased oxidative stress, cell damage, cell death, and apoptosis, while OA treatment miti-gated these TNF-α induced effects.
We concluded that TNF-α is implicated in the progression of heart failure subsequent to MI and that OA in olive oil may prevent this progression, through its anti-oxidant, anti-inflammatory, anti-hypertensive, and inotropic effects.
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Miyamoto, Shoichi. "Histone acetyltransferase activity of p300 is required for the promotion of left ventricular remodeling following myocardial infarction in adult mice in vivo." Kyoto University, 2006. http://hdl.handle.net/2433/143836.
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Silveira, Caroline Ferreira da Silva Mazeto Pupo da. "Preditores clínicos e ecocardiográficos de remodelação ventricular esquerda após infarto agudo do miocárdio de parede anterior." Botucatu, 2019. http://hdl.handle.net/11449/182426.
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Orientador: Silméia Garcia Zanati BazanResumo: Introdução: A doença arterial coronariana é a primeira causa isolada de morte e responsável por elevado número de hospitalizações em todo o mundo. O desenvolvimento de remodelação ventricular está associado com pior prognóstico após o infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCST), representando fator de risco para a disfunção ventricular e insuficiência cardíaca. Objetivos: Identificar quais variáveis são preditoras da remodelação ventricular após o IAMCST e avaliar as características clínicas, laboratoriais e ecocardiográficas em pacientes na fase aguda do IAMCST de parede anterior submetidos à angioplastia primária e após seis meses do infarto. Metodologia: Foi realizado um estudo prospectivo, observacional e longitudinal, composto por pacientes com diagnóstico de IAMCST de parede anterior admitidos na Unidade Coronariana (UCO) do Hospital das Clínicas da Faculdade de Medicina de Botucatu no período de julho de 2017 a agosto de 2018. Foram incluídos 50 pacientes, sendo que quatro perderam o seguimento em seis meses e cinco evoluíram a óbito no mesmo período. Durante o período da internação na UCO, os pacientes foram avaliados diariamente e submetidos ao primeiro ecocardiograma em 2 a 3 dias após o IAMCST. No sexto mês após o IAMCST, os pacientes foram submetidos à reavaliação clínica e a novo ecocardiograma, conforme protocolo do serviço. A remodelação cardíaca foi considerada como aumento no volume diastólico superior a 15%. Análise estatística... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Introduction: Coronary arterial disease is the first isolated death cause and is responsible for an elevated number of hospitalizations all over the world. The development of ventricular remodeling is associated with worse prognosis after ST segment elevation myocardial infarction (STEMI), representing a risk factor for ventricular dysfunction and heart failure. Objectives: To identify which variables are predictors of ventricular remodeling after STEMI and to evaluate clinical, laboratorial and echocardiographic characteristics of patients early post anterior STEMI who went through primary percutaneous intervention and six month after infarction. Methods: This was a prospective, observational and longitudinal study, with anterior STEMI patients admitted to the coronary care unit (CCU) of the Botucatu Medical School Clinics Hospital within July 2017 and August 2018. A total of 50 patients were included, four lost follow-up in six months and five died within the same period. During CCU stay, patients were daily evaluated and submitted to an echocardiogram within the first three days after STEMI. After six months, patients were submitted to a new clinical evaluation and a new echocardiogram, according to local protocol. Ventricular remodeling was considered as a raise in diastolic volume greater than 15%. Statistical analysis: continuous variable both normal and non-normal distribution were presented in either average and standard deviation or median and 25 and 75 percentiles, ... (Complete abstract click electronic access below)
Mestre
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Santana, Eduardo Tadeu. "Caracterização da expressão gênica de vias de transdução do sinal no miocárdio remoto ao infarto induzido por ablação ventricular esquerda e oclusão da artéria coronária em ratos." Universidade Nove de Julho, 2015. http://bibliotecatede.uninove.br/handle/tede/1824.
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The ligation of the anterior descending coronary artery is the most commonly used experimental model to induce myocardial infarction (MI) in rodents. A high mortality in the acute phase and the heterogeneity of the size of the MI obtained are drawbacks recognized in this model. In an attempt to solve the problem, our group recently developed a new MI experimental model which is based on application of myocardial ablation radio-frequency currents (AB-RF) that yielded MI with homogeneous sizes and significantly reduce acute mortality. In addition, cardiac structural and functional changes aroused by AB-RF were similar to those seen in animals with MI induced by coronary artery ligation. Herein, we evaluated modifications of gene expression that govern post-MI milieu in occlusion and ablation models. We analyzed 48 mRNA expressions of 9 different signal transduction pathways (signs of cell survival and metabolism, matrix extracellular, cell cycle, oxidative stress, apoptosis, calcium signaling, hypertrophy markers, angiogenesis and inflammation) in rat left ventricle 1 week after MI promoted by either coronary occlusion and AB-RF. Furthermore, high-throughput miRNA analysis was also assessed after either MI procedures. Interestingly, mRNA expression levels and miRNA expressions were similar in both models after MI, with few specificities in each model. This study reports for the first time the global changes in rat cardiac mRNA and miRNA contents after two different MI procedures and identifies key signaling regulators modulating the pathophysiology of these two models that might culminate in heart failure. Furthermore, these analyses would enhance our present knowledge regarding altered pathophysiology of these two different MI models.
A ligadura da artéria coronariana descendente anterior é o modelo experimental mais comumente usado para induzir o infarto do miocárdio (IM) em roedores. Entretanto, uma elevada taxa de mortalidade na fase aguda e a heterogeneidade do tamanho do IM obtidos são desvantagens reconhecidas neste modelo. Em uma tentativa de resolver o problema, o nosso grupo desenvolveu recentemente um novo modelo experimental de insuficiência cardíaca que se baseia na aplicação de correntes de radiofrequência ablação do miocárdio (AB-RF), produzindo IM com tamanhos homogêneos e com significativamente redução da mortalidade aguda. Além disso, alterações estruturais e funcionais do coração deste modelo foram semelhantes aos observados em animais com infarto induzido por ligação da artéria coronária. Aqui, nós avaliamos modificações da expressão de RNA mensageiro (RNAm) de genes após IM induzido por oclusão e ablação. Foram analisadas as expressões de 48 RNAm de 9 diferentes vias de transdução de sinal (sinais de sobrevivência celular e metabolismo, matriz extracelular, ciclo celular, estresse oxidativo, apoptose, sinalização de cálcio, marcadores de hipertrofia, angiogênese e inflamação) no ventrículo esquerdo de ratos uma semana após o IM promovido por oclusão coronária e AB-RF. Além disso, a análise de alto rendimento de miRNA também foi avaliada após ambos procedimentos de IM. Curiosamente, os níveis de expressão de RNAm e expressão de miRNA foram semelhantes em ambos os modelos após o IM, com algumas especificidades em cada modelo. Este estudo relata pela primeira vez as mudanças globais nos conteúdos de RNAm e miRNA após dois procedimentos de IM diferentes e identifica reguladores que podem modular a fisiopatologia desses dois modelos, culminando em insuficiência cardíaca.
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Lauer, Dilyara [Verfasser]. "Prevention of cardiac remodeling after experimental myocardial infarction. Role of the angiotensin II type 2 receptor stimulation and modulation of MMP/TIMP axis / Dilyara Lauer." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2016. http://d-nb.info/1119803527/34.
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Weirather, Johannes [Verfasser], Stefan [Gutachter] Frantz, Ingolf [Gutachter] Berberich, and Thomas [Gutachter] Kerkau. "Role of CD4+ T lymphocytes in cardiac wound healing and remodeling after experimental myocardial infarction in mice / Johannes Weirather. Gutachter: Stefan Frantz ; Ingolf Berberich ; Thomas Kerkau." Würzburg : Universität Würzburg, 2014. http://d-nb.info/1108781004/34.
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