Academic literature on the topic 'Vascular smooth muscle cell phenotypic switch'
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Journal articles on the topic "Vascular smooth muscle cell phenotypic switch"
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Tang, Yangfeng, Shangyi Yu, Yang Liu, Jiajun Zhang, Lin Han, and Zhiyun Xu. "MicroRNA-124 controls human vascular smooth muscle cell phenotypic switch via Sp1." American Journal of Physiology-Heart and Circulatory Physiology 313, no. 3 (2017): H641—H649. http://dx.doi.org/10.1152/ajpheart.00660.2016.
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Phenotypic switch of vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of atherosclerosis and aortic dissection. However, the mechanisms of phenotypic modulation are still unclear. MicroRNAs have emerged as important regulators of VSMC function. We recently found that microRNA-124 (miR-124) was downregulated in proliferative vascular diseases that were characterized by a VSMC phenotypic switch. Therefore, we speculated that the aberrant expression of miR-124 might play a critical role in human aortic VSMC phenotypic switch. Using quantitative RT-PCR, we found that miR-124 was dramatically downregulated in the aortic media of clinical specimens of the dissected aorta and correlated with molecular markers of the contractile VSMC phenotype. Overexpression of miR-124 by mimicking transfection significantly attenuated platelet-derived growth factor-BB-induced human aortic VSMC proliferation and phenotypic switch. Furthermore, we identified specificity protein 1 (Sp1) as the downstream target of miR-124. A luciferase reporter assay was used to confirm direct miR-124 targeting of the 3′-untranslated region of the Sp1 gene and repression of Sp1 expression in human aortic VSMCs. Furthermore, constitutively active Sp1 in miR-124-overexpressing VSMCs reversed the antiproliferative effects of miR-124. These results demonstrated a novel mechanism of miR-124 modulation of VSMC phenotypic switch by targeting Sp1 expression. NEW & NOTEWORTHY Previous studies have demonstrated that miR-124 is involved in the proliferation of a variety of cell types. However, miRNAs are expressed in a tissue-specific manner. We first identified miR-124 as a critical regulator in human aortic vascular smooth muscle cell differentiation, proliferation, and phenotype switch by targeting the 3′-untranslated region of specificity protein 1.
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Badran, Adnan, Suzanne A. Nasser, Joelle Mesmar, et al. "Reactive Oxygen Species: Modulators of Phenotypic Switch of Vascular Smooth Muscle Cells." International Journal of Molecular Sciences 21, no. 22 (2020): 8764. http://dx.doi.org/10.3390/ijms21228764.
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Reactive oxygen species (ROS) are natural byproducts of oxygen metabolism in the cell. At physiological levels, they play a vital role in cell signaling. However, high ROS levels cause oxidative stress, which is implicated in cardiovascular diseases (CVD) such as atherosclerosis, hypertension, and restenosis after angioplasty. Despite the great amount of research conducted to identify the role of ROS in CVD, the image is still far from being complete. A common event in CVD pathophysiology is the switch of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. Interestingly, oxidative stress is a major contributor to this phenotypic switch. In this review, we focus on the effect of ROS on the hallmarks of VSMC phenotypic switch, particularly proliferation and migration. In addition, we speculate on the underlying molecular mechanisms of these cellular events. Along these lines, the impact of ROS on the expression of contractile markers of VSMCs is discussed in depth. We conclude by commenting on the efficiency of antioxidants as CVD therapies.
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Sun, Huiyan, Songzhi Cai, Mei Zhang, et al. "MicroRNA-206 regulates vascular smooth muscle cell phenotypic switch and vascular neointimal formation." Cell Biology International 41, no. 7 (2017): 739–48. http://dx.doi.org/10.1002/cbin.10768.
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Li, Pan, Ni Zhu, Bing Yi, et al. "MicroRNA-663 Regulates Human Vascular Smooth Muscle Cell Phenotypic Switch and Vascular Neointimal Formation." Circulation Research 113, no. 10 (2013): 1117–27. http://dx.doi.org/10.1161/circresaha.113.301306.
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Miano, Joseph M., Edward A. Fisher, and Mark W. Majesky. "Fate and State of Vascular Smooth Muscle Cells in Atherosclerosis." Circulation 143, no. 21 (2021): 2110–16. http://dx.doi.org/10.1161/circulationaha.120.049922.
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Vascular smooth muscle cells (VSMCs) have long been associated with phenotypic modulation/plasticity or dedifferentiation. Innovative technologies in cell lineage tracing, single-cell RNA sequencing, and human genomics have been integrated to gain unprecedented insights into the molecular reprogramming of VSMCs to other cell phenotypes in experimental and clinical atherosclerosis. The current thinking is that an apparently small subset of contractile VSMCs undergoes a fate switch to transitional, multipotential cells that can adopt plaque-destabilizing (inflammation, ossification) or plaque-stabilizing (collagen matrix deposition) cell states. Several candidate mediators of such VSMC fate and state changes are coming to light with intriguing implications for understanding coronary artery disease risk and the development of new treatment modalities. Here, we briefly summarize some technical and conceptual advancements derived from 2 publications in Circulation and another in Nature Medicine that, collectively, illuminate new research directions to further explore the role of VSMCs in atherosclerotic disease.
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Liao, Xing-Hua, Nan Wang, Dong-Wei Zhao, et al. "STAT3 Protein Regulates Vascular Smooth Muscle Cell Phenotypic Switch by Interaction with Myocardin." Journal of Biological Chemistry 290, no. 32 (2015): 19641–52. http://dx.doi.org/10.1074/jbc.m114.630111.
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Xie, Changqing, Yanhong Guo, Tianqing Zhu, Jifeng Zhang, Peter X. Ma, and Y. Eugene Chen. "Yap1 Protein Regulates Vascular Smooth Muscle Cell Phenotypic Switch by Interaction with Myocardin." Journal of Biological Chemistry 287, no. 18 (2012): 14598–605. http://dx.doi.org/10.1074/jbc.m111.329268.
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Green, Immanuel D., Renjing Liu, and Justin J. L. Wong. "The Expanding Role of Alternative Splicing in Vascular Smooth Muscle Cell Plasticity." International Journal of Molecular Sciences 22, no. 19 (2021): 10213. http://dx.doi.org/10.3390/ijms221910213.
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Vascular smooth muscle cells (VSMCs) display extraordinary phenotypic plasticity. This allows them to differentiate or dedifferentiate, depending on environmental cues. The ability to ‘switch’ between a quiescent contractile phenotype to a highly proliferative synthetic state renders VSMCs as primary mediators of vascular repair and remodelling. When their plasticity is pathological, it can lead to cardiovascular diseases such as atherosclerosis and restenosis. Coinciding with significant technological and conceptual innovations in RNA biology, there has been a growing focus on the role of alternative splicing in VSMC gene expression regulation. Herein, we review how alternative splicing and its regulatory factors are involved in generating protein diversity and altering gene expression levels in VSMC plasticity. Moreover, we explore how recent advancements in the development of splicing-modulating therapies may be applied to VSMC-related pathologies.
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Bonetti, Justine, Alessandro Corti, Lucie Lerouge, Alfonso Pompella, and Caroline Gaucher. "Phenotypic Modulation of Macrophages and Vascular Smooth Muscle Cells in Atherosclerosis—Nitro-Redox Interconnections." Antioxidants 10, no. 4 (2021): 516. http://dx.doi.org/10.3390/antiox10040516.
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Monocytes/macrophages and vascular smooth muscle cells (vSMCs) are the main cell types implicated in atherosclerosis development, and unlike other mature cell types, both retain a remarkable plasticity. In mature vessels, differentiated vSMCs control the vascular tone and the blood pressure. In response to vascular injury and modifications of the local environment (inflammation, oxidative stress), vSMCs switch from a contractile to a secretory phenotype and also display macrophagic markers expression and a macrophagic behaviour. Endothelial dysfunction promotes adhesion to the endothelium of monocytes, which infiltrate the sub-endothelium and differentiate into macrophages. The latter become polarised into M1 (pro-inflammatory), M2 (anti-inflammatory) or Mox macrophages (oxidative stress phenotype). Both monocyte-derived macrophages and macrophage-like vSMCs are able to internalise and accumulate oxLDL, leading to formation of “foam cells” within atherosclerotic plaques. Variations in the levels of nitric oxide (NO) can affect several of the molecular pathways implicated in the described phenomena. Elucidation of the underlying mechanisms could help to identify novel specific therapeutic targets, but to date much remains to be explored. The present article is an overview of the different factors and signalling pathways implicated in plaque formation and of the effects of NO on the molecular steps of the phenotypic switch of macrophages and vSMCs.
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Pung, Yuh Fen, Wai Johnn Sam, James P. Hardwick, et al. "The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth." American Journal of Physiology-Heart and Circulatory Physiology 305, no. 9 (2013): H1275—H1280. http://dx.doi.org/10.1152/ajpheart.00077.2013.
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Coronary collateral growth is a process involving coordination between growth factors expressed in response to ischemia and mechanical forces. Underlying this response is proliferation of vascular smooth muscle and endothelial cells, resulting in an enlargement in the caliber of arterial-arterial anastomoses, i.e., a collateral vessel, sometimes as much as an order of magnitude. An integral element of this cell proliferation is the process known as phenotypic switching in which cells of a particular phenotype, e.g., contractile vascular smooth muscle, must change their phenotype to proliferate. Phenotypic switching requires that protein synthesis occurs and different kinase signaling pathways become activated, necessitating energy to make the switch. Moreover, kinases, using ATP to phosphorylate their targets, have an energy requirement themselves. Mitochondria play a key role in the energy production that enables phenotypic switching, but under conditions where mitochondrial energy production is constrained, e.g., mitochondrial oxidative stress, this switch is impaired. In addition, we discuss the potential importance of uncoupling proteins as modulators of mitochondrial reactive oxygen species production and bioenergetics, as well as the role of AMP kinase as an energy sensor upstream of mammalian target of rapamycin, the master regulator of protein synthesis.
Dissertations / Theses on the topic "Vascular smooth muscle cell phenotypic switch"
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Chen, Pei-Yu. "Fibroblast Growth Factor Receptor-1 (FGFR1) in Vascular Smooth Muscle Cell Phenotypic Switch." Fogler Library, University of Maine, 2009. http://www.library.umaine.edu/theses/pdf/ChenPY2009.pdf.
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Harman, Jennifer. "Investigating the role of histone H3 lysine 9 dimethylation in regulating disease-associated vascular smooth muscle cell gene expression." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/289975.
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Widespread changes in gene expression accompany vascular smooth muscle cell (VSMC) phenotypic switching, a hallmark of vascular disease. Upon insult, VSMCs downregulate contractile proteins and upregulate genes linked to vascular remodelling, such as matrix metalloproteinases (MMPs) and pro-inflammatory cytokines. However, the epigenetic mechanisms which regulate VSMC phenotypic switching remain unclear. This thesis explores the role of histone 3 lysine 9 dimethylation (H3K9me2), a repressive epigenetic mark, in regulating the expression of disease-associated VSMC genes. Intriguingly, murine models of VSMC phenotypic switching revealed reduced levels of H3K9me2 upon loss of the contractile state while chromatin immunoprecipitation (ChIP) identified a subset of IL-1α/injury-responsive VSMC gene promoters enriched for H3K9me2. To test the functional importance of H3K9me2 for VSMC gene regulation the methyltransferase G9A/GLP was pharmacologically inhibited in vitro and in vivo. The resulting loss of H3K9me2 attenuated the expression of contractile VSMC markers and significantly potentiated IL-1α/injury-induced expression of MMP and pro-inflammatory genes. H3K9me2-mediated regulation of contractile and IL-1α-responsive VSMC gene expression was confirmed in cultured human VSMCs (hVSMCs). This prompted the use of hVSMCs to investigate the mechanism underlying H3K9me2-dependent regulation of IL-1α-mediated VSMC genes. Interestingly, G9A/GLP inhibition did not influence the level of IL-1α-induced nuclear localisation of the NFkB transcription factor p65 but significantly increased IL-1α-induced p65 binding to the IL6 promoter, correlating with reduced H3K9me2 levels. In contrast, enrichment of p65 was not observed at reported NFkB sites within the MMP3 promoter after IL-1α stimulation. Rather, IL-1α-induced MMP3 expression was dependent on JNK activity and G9A/GLP inhibition potentiated IL-1α-induced binding of the AP-1 transcription factor cJUN to the MMP3 promoter. Collectively, these findings suggest that H3K9me2 plays a role in maintaining the contractile VSMC state and prevents binding of both NFkB and AP-1 transcription factors at specific IL-1α-regulated genes to possibly block spurious induction of a pro-inflammatory state.
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Dinh, Kristie Nhi. "Interleukin-2 Receptor Alpha Nuclear Localization Impacts Vascular Smooth Muscle Cell Function and Phenotype." Wright State University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=wright1630243625985423.
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Adedoyin, Oreoluwa O. "MECHANISMS OF CYCLOOXYGENASE-2-DEPENDENT HUMAN AORTIC SMOOTH MUSCLE CELL PHENOTYPIC MODULATION." UKnowledge, 2014. http://uknowledge.uky.edu/pharmacy_etds/34.
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Abdominal aortic aneurysm (AAA) is a disease of the aorta characterized by pathological remodeling and progressive weakening of the vessel resulting in the increased risk of rupture and sudden death. In a mouse model of the disease induced by chronic Angiotensin II (AngII) infusion, progression of AAAs is associated with reduced differentiation of smooth muscle cells (SMCs) at the site of lesion development. In the mouse model, the effectiveness of cyclooxygenase-2 (COX-2) inhibition for attenuating AAA progression is associated with maintenance of a differentiated SMC phenotype. However, the safety of COX-2 inhibitors is currently in question due to the increased risk of adverse cardiovascular events. Thus, it is crucial to identify mediators downstream of COX-2 that may provide new targets for treatment of this disease.
Recent studies in humans and mouse models have suggested that the microsomal prostaglandin E synthase (mPGES-1) enzyme, which acts downstream of COX-2, may also be involved in the pathogenesis of the disease. We hypothesized that increased prostaglandin E2 (PGE2) synthesis resulting from the induction of both COX-2 and mPGES-1 may result in reduced differentiation of SMCs, and that disruption of this pathway would preserve the differentiated phenotype. To test this hypothesis, human aortic smooth muscle cells (hASMCs) were utilized to examine the effects of a variety of agents involved in AAA development and the COX-2 pathway.
My findings suggest that one of the effects of exposing hASMCs to AngII involves a specific induction of mPGES-1 expression. Furthermore, although different COX-2-derived products may have opposing effects, mPGES-1-derived PGE2 may be the primary prostanoid synthesized by SMCs which functions to attenuate differentiation. Therefore, mPGES-1 inhibition may provide inhibition of PGE2 that is more specific than COX-2 inhibitor treatment and may serve as a therapeutic target for attenuating AAA progression by maintaining a differentiated SMC phenotype.
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Tharp, Darla L. "Role of the intermediate-conductance Ca²⁺-activated K⁺ channel (K[ca]3.1) in coronary smooth muscle cell phenotypic modulation." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/5936.
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Thesis (Ph. D.)--University of Missouri-Columbia, 2007.<br>The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "December 2007" Includes bibliographical references.
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Tsai, Min-Chien, and 蔡旻倩. "Molecular Mechanisms of Phenotypic Modulation of Vascular Smooth Muscle Cells: A Study of Endothelial Cell-Smooth Muscle Cell Interaction in Response to Fluid Shear Stress." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/37008580968018301648.
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博士<br>國防醫學院<br>生命科學研究所<br>98<br>Phenotypic modulation of smooth muscle cells (SMCs), which are located in close proximity to endothelial cells (ECs), is critical in regulating vascular function. We investigated the role of blood flow-induced shear stress on ECs in modulating SMC phenotype and its underlying mechanism, using an EC/SMC co-culture flow system in which ECs and SMCs were separated by a porous membrane. Application of shear stress (12 dynes/cm2) to EC/SMC modulated SMC phenotype from synthetic to contractile state, with increased expressions of contractile markers smooth muscle--actin, myosin heavy chain, calponin, h-caldesmon, and protein 22-, and decreased expressions of pro-inflammatory factors monocyte chemotactic protein-1 and interleukin-8. Treating SMCs with media from sheared ECs induced peroxisome proliferator-activated receptor (PPAR)-, -, and - ligand binding activities; transfecting SMCs with specific small interfering RNAs (siRNAs) of PPAR-a and -d, but not -g, inhibited shear-induction of contractile markers. ECs exposed to shear stress released prostacyclin (PGI2). Transfecting ECs with PGI2 synthase-specific siRNA inhibited the shear-induced activation of PPAR- and -, up-regulation of contractile markers, down-regulation of pro-inflammatory genes and decrease in percentage of SMCs in synthetic phase. Mice with PPAR- deficiency showed altered SMC phenotype toward a synthetic state, with increased arterial contractility in response to angiotensin II, as compared with control littermates. These results indicate that laminar shear stress induces synthetic-to-contractile phenotypic modulation in SMCs through the activation of PPAR-/ by the EC-released PGI2. Our findings provide insights into the mechanisms underlying the interplays of ECs with SMCs and the protective homeostatic function of laminar shear stress in modulating SMC phenotype.
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CHYOU, CHIEN-CHEN, та 邱建禎. "Role Of RAGE And CTGF In PPAR-δ Regulates Vascular Smooth Muscle Cell Phenotypic Modulation Under Diabetic Atherosclerosis Model". Thesis, 2016. http://ndltd.ncl.edu.tw/handle/82678876399036922856.
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碩士<br>國防醫學院<br>生理學研究所<br>104<br>Diabetes mellitus patients have a high risk of cardiovascular disease such like atherosclerosis. In past few years, it’s believed that the reason why Diabetes mellitus patients have risk for cardiovascular disease is due to the metabolic abnormalities due to diabetes, hyperglycemia and hyperlipidemia. But in recent year, some researches indicate that the phenotype of vascular smooth muscle cells (VSMCs) in diabetes patients is under synthetic phenotype.
Phenotypic modulation of VSMCs plays a critical role in regulate the function of vascular. During the progression of atherosclerosis, VSMC change from physiological contractile phenotype to pathophysiological synthesis phenotype. Past few years, there is more evidence that both receptor for advanced glycation end products (RAGE) and connective tissue growth factor (CTGF) play a critical role in VSMCs migration and proliferation. Also, expression of RAGE and CTGF will increase under diabetes mellitus, but whether RAGE and CTGF can modulate VSMCs phenotypic modulation under diabetes condition are stay unclear. On the other hand, it is clear that peroxisome proliferator-activated receptor δ (PPAR δ) can modulate VSMCs phenotypic modulation, however the mechanism responsible for the phenotypic modulation are unclear. In addition, PPAR δ can inhibit the expression of RAGE in kidney, but whether the same effect work in aorta is still unclear.
In this study, we use apolipoprotein E knockout mice (ApoE KO mice) induce diabetes, and treat with PPARδ agonist GW501516. We found out that treatment of GW501516 inhibit the expression of RAGE, CTGF and synthetic protein vimentin. Also we found out that treat human aortic smooth muscle cells with AGE and CTGF recombinant protein can increase the expression of synthetic protein, vimentin, and decrease the expression of contractile protein, myosin heavy chain and h-caldesmon. We also found out that treat HASMCs with GW501516 can decrease the expression of RAGE and switch the VSMCs to contractile phenotype. In conclusion, PPARδ can prevent VSMCs switch to synthetic phenotype by inhibit the expression of RAGE.
Books on the topic "Vascular smooth muscle cell phenotypic switch"
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Badimon, Lina, and Gemma Vilahur. Atherosclerosis and thrombosis. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199687039.003.0040.
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Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the extracellular matrix and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated monocytes differentiate into macrophages which acquire a specialized phenotypic polarization (protective or harmful), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoprotein via low-density lipoprotein receptor-related protein-1 receptors. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Both lipid-laden vascular smooth muscle cells and macrophages release the procoagulant tissue factor, contributing to thrombus propagation. Platelets also participate in progenitor cell recruitment and drive the inflammatory response mediating the atherosclerosis progression. Recent data attribute to microparticles a potential modulatory effect in the overall atherothrombotic process. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be modulated.
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Badimon, Lina, and Gemma Vilahur. Atherosclerosis and thrombosis. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199687039.003.0040_update_001.
Full textAbstract:
Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the intimal layer and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles attached to the extracellular matrix suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated pro-atherogenic monocytes (mainly Mon2) differentiate into macrophages which acquire a specialized phenotypic polarization (protective/M1 or harmful/M2), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoproteins via low-density lipoprotein receptor-related protein-1 receptors becoming foam cells. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels and calcium deposits increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces rich in tissue factor that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Platelets also participate in leucocyte and progenitor cell recruitment are likely to mediate atherosclerosis progression. Recent data attribute to microparticles a modulatory effect in the overall atherothrombotic process and evidence their potential use as systemic biomarkers of thrombus growth. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be prevented and modulated.
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Badimon, Lina, and Gemma Vilahur. Atherosclerosis and thrombosis. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199687039.003.0040_update_002.
Full textAbstract:
Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the intimal layer and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles attached to the extracellular matrix suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated pro-atherogenic monocytes (mainly Mon2) differentiate into macrophages which acquire a specialized phenotypic polarization (protective/M1 or harmful/M2), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoproteins via low-density lipoprotein receptor-related protein-1 receptors becoming foam cells. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels and calcium deposits increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces rich in tissue factor that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Platelets also participate in leucocyte and progenitor cell recruitment are likely to mediate atherosclerosis progression. Recent data attribute to microparticles a modulatory effect in the overall atherothrombotic process and evidence their potential use as systemic biomarkers of thrombus growth. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be prevented and modulated.
Book chapters on the topic "Vascular smooth muscle cell phenotypic switch"
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Owens, Gary K. "Molecular Control of Vascular Smooth Muscle Cell Differentiation and Phenotypic Plasticity." In Vascular Development. John Wiley & Sons, Ltd, 2007. http://dx.doi.org/10.1002/9780470319413.ch14.
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Miano, Joseph M. "Vascular Smooth Muscle Cell Phenotypic Adaptation." In Muscle. Elsevier, 2012. http://dx.doi.org/10.1016/b978-0-12-381510-1.00095-8.
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Shimokawa, Hiroaki, and Jun Takahashi. "Coronary artery spasm." In State of the Art Surgical Coronary Revascularization, edited by David P. Taggart, John D. Puskas, and Mario Gaudino. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198758785.003.0005.
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Coronary artery spasm is a condition in which an epicardial coronary artery or coronary bypass graft exhibits abnormal transient constriction with the possible or subsequent development of myocardial ischaemia. Porcine models have demonstrated the important role of atherosclerotic/inflammatory changes of the coronary artery and established that hypercontraction of vascular smooth muscle cells plays a central role in the genesis of spasm and is, in part, dependent on activation of Rho-kinase, a molecular switch for vascular smooth muscle cell contraction. Fasudil, which is used for the treatment of cerebral vasospasm in Japan, is metabolized to hydroxyfasudil and functions as a selective Rho-kinase inhibitor. Recent studies demonstrated that inflammatory changes in the adventitia of the coronary artery play an important role for Rho-kinase activation of vascular smooth muscle cells. Prevention and treatment of coronary spasm is important in preventing acute coronary syndromes and sudden cardiac death.
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Badimon, Lina, and Gemma Vilahur. "Atherosclerosis and thrombosis." In The ESC Textbook of Intensive and Acute Cardiovascular Care, edited by Marco Tubaro, Pascal Vranckx, Eric Bonnefoy-Cudraz, Susanna Price, and Christiaan Vrints. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198849346.003.0037.
Full textAbstract:
Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the intimal layer and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles attached to the extracellular matrix suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated pro-atherogenic monocytes (mainly Mon2) differentiate into macrophages which acquire a specialized phenotypic polarization (protective/M1 or harmful/M2), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoproteins via low-density lipoprotein receptor-related protein-1 receptors becoming foam cells. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels and calcium deposits increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces rich in tissue factor that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Platelets also participate in leucocyte and progenitor cell recruitment are likely to mediate atherosclerosis progression. Recent data attribute to extracellular vesicles (mainly microvesicles) a role in all stages of atherosclerosis development and evidence their potential use as systemic biomarkers of thrombus growth. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be prevented and modulated.