Segui questo link per vedere altri tipi di pubblicazioni sul tema: Hypercholesterolemie.
Tesi sul tema "Hypercholesterolemie"
Cita una fonte nei formati APA, MLA, Chicago, Harvard e in molti altri stili
Vedi i top-50 saggi (tesi di laurea o di dottorato) per l'attività di ricerca sul tema "Hypercholesterolemie".
Accanto a ogni fonte nell'elenco di riferimenti c'è un pulsante "Aggiungi alla bibliografia". Premilo e genereremo automaticamente la citazione bibliografica dell'opera scelta nello stile citazionale di cui hai bisogno: APA, MLA, Harvard, Chicago, Vancouver ecc.
Puoi anche scaricare il testo completo della pubblicazione scientifica nel formato .pdf e leggere online l'abstract (il sommario) dell'opera se è presente nei metadati.
Vedi le tesi di molte aree scientifiche e compila una bibliografia corretta.
1
Boileau, Catherine, e J. P. GELOSO. "Syndrome de marfan et hypercholesterolemie : modeles d'heterogeneite genetique". Paris 7, 1993. http://www.theses.fr/1993PA077318.
Testo completoAbstract (sommario):
Le syndrome de marfan (sm) et l'hypercholesterolemie familiale (hf) correspondent a deux groupes de pathologies a transmission autosomique dominante pour lesquelles une heterogeneite genetique a longtemps ete soupconnee. Pour identifier les facteurs genetiques associes a ces maladies, nous avons utilise une approche combinant des methodes genetiques et moleculaires, appliquees tant a des analyses de familles que de populations. Par l'approche gene candidat utilisee dans l'etude d'une grande famille presentant une forme variante du sm, nous avons montre que, a la difference des formes classiques, la maladie n'etait pas liee au gene de la fibrilline (fib15). Ce resultat a conduit a la definition d'une nouvelle entite clinique et moleculaire. Apres l'exclusion de genes codant pour d'autres constituants de la matrice extracellulaire, nous avons entrepris une carte d'exclusion genomique qui a deja permis d'eliminer plus de 65% du genome. Dans le cas de l'hf, nous avons identifie 7 nouvelles mutations du gene du recepteur ldl (ldlr) demontrant ainsi une importante heterogeneite allelique. Nous avons aussi retrouve la mutation 3500 du gene de l'apo b (apob) chez un sujet. Cette mutation etait associee a un haplotype identique a celui rapporte chez d'autres proposants, confirmant la nature unique et europeenne de cette mutation. Par ailleurs, la liaison aux genes ldlr et apob a pu etre exclue dans une fraction importante de familles de hf, demontrant ainsi l'implication d'au moins un troisieme facteur genetique a effet dominant. Enfin, nous n'avons pas observe de desequilibre de liaison entre l'hypercholesterolemie et les marqueurs des genes apoa1-c3-a4. L'ensemble de ces resultats va maintenant etre suivie de l'identification des nouveaux facteurs genetiques impliques dans le sm et l'hf permettant ainsi de tendre vers des tests de diagnostic specifiques
2
BARRET, FRANCOISE. "Hypercholesterolemie familiale de l'enfant : a propos de deux observations". Limoges, 1988. http://www.theses.fr/1988LIMO0127.
Testo completo
3
COLOMES, MARYVONNE. "Hypercholesterolemies : etude de l'efficacite et de la tolerance de la fluvastatine". Toulouse 3, 1991. http://www.theses.fr/1991TOU31523.
Testo completo
4
DIEBOLT, PASCAL. "Les hypercholesterolemies : nouvelle approche therapeutique". Strasbourg 1, 1990. http://www.theses.fr/1990STR15042.
Testo completo
5
Bent, Patrick. "Lipides et qualites du sperme". Clermont-Ferrand 1, 1992. http://www.theses.fr/1992CLF13832.
Testo completo
6
DE, LA FARGE FLORENCE. "Interets du bilan lipidique chez le sujet age". Toulouse 3, 1992. http://www.theses.fr/1992TOU31126.
Testo completo
7
VANEL, NATHALIE. "L'hypercholesterolemie dans le sang du cordon humain : recherche d'une signification pronostique". Lyon 1, 1989. http://www.theses.fr/1989LYO1M480.
Testo completo
8
SETBON, JEAN-MARC. "L'hypercholesterolemie familiale homozygote : possibilites therapeutiques actuelles ; a propos de deux cas d'une meme fratrie". Aix-Marseille 2, 1989. http://www.theses.fr/1989AIX20046.
Testo completo
9
Chanial, Christine. "Incidence de l'hypothyroi͏̈die dans l'hypercholestérolémie : étude prospective sur 135 cas". Montpellier 1, 1991. http://www.theses.fr/1991MON11095.
Testo completo
10
FAUROUX, MARIE-FRANCOISE. "Etude comparative pravastatine : cholestyramine chez 67 patients atteints d'hypercholesterolemie familiale". Toulouse 3, 1989. http://www.theses.fr/1989TOU31033.
Testo completo
11
STOLL, AGNES. "Etude comparative synvinoline / fenofibrate chez 50 patients atteints d'hypercholesterolemie familiale". Toulouse 3, 1989. http://www.theses.fr/1989TOU31015.
Testo completo
12
Darrigrand, Olivier. "Nouvelle approche du cholestérol : à propos de six cas d'hypercholestérolémie familiale". Bordeaux 2, 1991. http://www.theses.fr/1991BOR2M001.
Testo completo
13
CARLA, MALPUECH HELENE. "Etude du traitement par echanges plasmatiques et lipoadsorption de deux cas d'hypercholesterolemie familiale homozygote". Clermont-Ferrand 1, 1991. http://www.theses.fr/1991CLF13808.
Testo completo
14
Nguyen, Thi Thanh Phuong. "L'hypercholestérolémie : traitements diététique et médicamenteux". Bordeaux 2, 1994. http://www.theses.fr/1994BOR2P028.
Testo completo
15
BRASCHI, OTT SYLVIE. "Desordres lipidiques rencontres dans l'analbuminemie congenitale : a propos de trois cas". Nantes, 1993. http://www.theses.fr/1993NANT243M.
Testo completo
16
MAGRI, GERARD. "Relations entre facteurs de risque cardiovasculaire et aspects anatomoradiologiques des arteres coronaires". Nice, 1993. http://www.theses.fr/1993NICE6527.
Testo completo
17
GIRARD, VALERIE. "Expression du genotype 10 kb dans l'hypercholesterolemie familiale heterozygote au quebec". Besançon, 1992. http://www.theses.fr/1992BESA3054.
Testo completo
18
SOUBIROUS, PHILIPPE. "Low-dentisty-lipoprotein apherese sur colonne de sulfate de dextran cellulose : etude chez 2 sujets hypercholesterolemiques". Toulouse 3, 1989. http://www.theses.fr/1989TOU31292.
Testo completo
19
Van, Belle Eric. "Modulation de la reponse des cellules endotheliales dans les phenomenes de reparation vasculaire : de la physiopathologie a la therapeutique (doctorat : cardiologie - appareil circulatoire)". Lille 2, 1997. http://www.theses.fr/1997LIL2T013.
Testo completo
20
Zureik, Mahmoud. "Cholesterolemie et mortalite par pathologies non cardio-vasculaires". Paris 11, 1997. http://www.theses.fr/1997PA11T002.
Testo completo
21
Trompe, Véronique. "Effets de la simvastatine sur les particules lipoprotéiniques chez des sujets présentant une hypercholestérolémie familiale". Paris 5, 1993. http://www.theses.fr/1993PA05P019.
Testo completo
22
Roubeix, Caroline. "Hypercholesterolémie athérosclérose et pravastatine". Bordeaux 2, 1993. http://www.theses.fr/1993BOR2PE79.
Testo completo
23
Frenais, Régis. "Etude cinetique du metabolisme de l'apo ai des hdl par les isotopes stables chez l'homme (doctorat : nutrition et metabolisme)". Nantes, 1999. http://www.theses.fr/1999NANT06VS.
Testo completo
24
Bouvelle, Anne. "Hypercholestérolémies, dyslipidémies : traitements et prévention". Paris 5, 1992. http://www.theses.fr/1992PA05P064.
Testo completo
25
Sallenave-Delprat, Claire. "Les nutriments réputés hypocholestérolémiants : inventaire et mode d'action". Bordeaux 2, 1997. http://www.theses.fr/1997BOR2M019.
Testo completo
26
Destriau, Tardy Emmanuelle. "Le statut plasmatique en antioxydants (vitamine A et E, b-carotène et sélénium) chez les sujets hypercholestérolémiques traités par LDL aphèrèse". Paris 5, 1997. http://www.theses.fr/1997PA05P072.
Testo completo
27
MAZOYER-LE, QUINIOU ELISABETH. "Modulation des fonctions plaquettaires par des elements stimulant (hypercholesterolemie) ou inhibant (peptides du lait) la formation de la thrombose arterielle. Etudes in vitro et in vivo". Paris 7, 1992. http://www.theses.fr/1992PA077264.
Testo completoAbstract (sommario):
Les plaquettes interviennent dans le processus de l'athero-thrombose. La thrombose arterielle survient dans des conditions hemodynamiques retrouvees au cours de l'atherosclerose secondaire a une hypercholesterolemie. Dans un premier temps et dans le but de detecter, par tomographie par emission de positons (tep), des lesions arterielles chez le lapin normal ou rendu hypercholesterolemique, les plaquettes ont ete marquees au gallium 68. La viabilite des plaquettes normales marquees a ete appreciee, comparativement a une technique de reference, avec un autre isotope, le gallium 67, dont la demie-vie s'adapte a cette mesure. Parallelement des etudes de morphologie, de biochimie, de cinetique et de fonctionnalite des plaquettes de ces lapins hypercholesterolemiques ont ete realisees. Elles objectivent une microthrombocytose, une modification de la composition lipidique de la membrane, une hypersensibilite aux faibles doses de collagene, associees a une diminution de la duree de vie de ces plaquettes. La thrombose arterielle peut etre prevenue par des molecules (peptides ou anticorps monoclonaux) agissant au niveau de l'interaction plaquette-fibrinogene. Dans un second temps, nous avons donc etudie l'activite d'un tetrapeptide de la lactotransferrine humaine, le krds, sur les fonctions des plaquettes humaines, et compare a celle d'un tetrapeptique de reference du fibrinogene humain, le rgds. In vitro, le krds inhibe l'agregation plaquettaire a l'adp et a la thrombine ainsi que la secretion dependante de la thrombine. L'activite inhibitrice sur la thrombogenese in vivo, chez le rat et le cobaye, suggere que le krds puisse devenir une molecule antithrombotique
28
Tarouel, Philippe. "L'Hypercholestérolémie est-elle corrélée à la consommation de cholestérol ou d'acides gras ? : étude de 40 patients à partir d'un logiciel de nutrition". Bordeaux 2, 1993. http://www.theses.fr/1993BOR2M124.
Testo completo
29
Sebbag, Carole. "L'hypercholestérolémie et les inhibiteurs de l'HMG CoA réductase". Paris 5, 1993. http://www.theses.fr/1993PA05P119.
Testo completo
30
Mrejen, Marie. "Place de l'arginine dans les propriétés anti-athéromateuses des protéines végétales". Paris 5, 2001. http://www.theses.fr/2001PA05P001.
Testo completo
31
Rubinsztein, David Chaim. "Monogenic hypercholesterolemia in South Africans : familial hypercholesterolemia in Indians and familial defective apolipoprotein B-100". Doctoral thesis, University of Cape Town, 1993. http://hdl.handle.net/11427/27142.
Testo completoAbstract (sommario):
LDL-receptor mutations and familial defective apolipoprotein B-100 (codon 3500) (FOB), the known causes of monogenic hypercholesterolemia (MH), have similar clinical features. The nature of the mutations responsible for MH in South Africans of Indian origin was previously unknown. Similarly, the mutations in the LDL-receptor gene of a South African Black FH homozygote had also not been characterised. The aim of this thesis was to identify and analyse the LDL-receptor mutations in the Indian homozygotes NS, D, AV and AA and in the Black homozygote JL. In addition, the possible importance of FOB as a cause of MH in South Africans was also assessed. The patient NS was characterized as having two "Null" LDL-receptor alleles. His skin fibroblasts expressed no detectable LDL-receptor protein and very low levels of LDL-receptor mRNA of approximately normal size. Since NS' s LDLreceptor promoter sequence was normal, his alleles are likely to harbour exonic point mutations or minor rearrangements that cause premature stop codons. The patient D was found to be a heteroallelic homozygote. Two new point mutations in the LDL receptor, Asp₆₉ -Tyr and Glu₁₁₉-Lys, were identified. D's fibroblasts expressed about 30% of the normal surf ace complement of receptors that bound LDL poorly. This low number could at least be partially explained by their decreased stability. These mutations were not identified in any other Indian FH or hypercholesterolemic patients. Patients AV and AA were both shown to be homoallelic homozygotes for the Pro₆₆₄ -Leu mutation. This mutation was identified in 4 unrelated Muslim families of Gujerati origin suggesting that the mutation arose from this area in India. Contrary to previous reports (Knight et al. 1990, Soutar et al. 1989), neither LOL nor β-VLDL binding were shown to be affected by this mutation. These mutant receptors were rapidly degraded. Thus the disease FH in these subjects is presumably due to the low steady-state level of mature receptors that are functionally normal but exhibit accelerated turnover. The Pedi FH homozygote, JL, expressed very few LOL receptors due to decreased receptor synthesis associated with low mRNA levels and not due to enhanced degradation. One of JL's LOL receptor alleles has a 3 b.p. deletion in repeat 1 of the promoter (G. Zuilani, H. Hobbs and L.F. de Waal, personal communication). The nature of the defect in his other allele is unknown. The importance of FOB as a cause of monogenic hypercholesterolemia in the South African Indian, "Coloured" and Afrikaner populations was determined by screening hypercholesterolemic subjects with or without xanthomata. The absence of FOB in such patients, in whom the relevant common or founder South African mutations were excluded, suggested that this disorder was rarer in these groups than in North America and Europe. FOB was identified in two different families of mixed British and Afrikaner ancestry. One family contained individuals who were heterozygous for the FOB mutation, as well as the FH Afrikaner-1 and the FH Afrikaner-2 LOL-receptor mutations. In addition, 4 compound heterozygotes, who had both FOB and the FH Afrikaner-1 mutation and one individual whu inherited all 3 defects, were identified. This family allowed us to characterise the compound heterozygotes with one mutant LOLreceptor allele and FOB as having a condition that was probably intermediate in severity between the FH heterozygote and homozygote states.
32
Farnaghi, Saba. "Role of hypercholesterolemia in osteoarthritis development". Thesis, Queensland University of Technology, 2017. https://eprints.qut.edu.au/103634/1/Saba_Farnaghi_Thesis.pdf.
Testo completoAbstract (sommario):
Several lines of research indicate that osteoarthritis (OA) is not only a joint disorder associated with mechanical stress and aging but also a ‘metabolic syndrome’ in which several risk factors work together to contribute to disease initiation and/or development. One such metabolic risk factor could be high cholesterol levels in the body. Even though high cholesterol level is a well-known risk factor for cardiovascular disorders, its possible role in musculoskeletal diseases, particularly OA, is not clear. The authors discuss the fundamental viewpoints on cholesterol involvement in the pathogenesis of OA, stressing the need for understanding the molecular mechanisms behind this association.
33
Grewal, Navdeep. "The link between hypercholesterolemia and tendon pathology". Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/44472.
Testo completoAbstract (sommario):
Tendinopathy is a major cause of morbidity in athletic populations and in the work force, traditionally thought to occur as a consequence of an imbalance between damage (resulting from mechanical loading) and repair. However, one third of the cases for midportion Achilles tendinopathy occur in sedentary individuals, and recent data suggests an association between hypercholesterolemia and the occurrence of tendon rupture or tendinopathy. The aim of this study was to examine the link between elevated lipids and tendon pathology. We used an apolipoprotein E-knockout model (ApoE-KO), in which apolipoprotein E deficiency leads to development of atherosclerosis. We hypothesized that tendons from ApoE-KO mice fed a high fat diet, in comparison to those fed a regular chow diet and the wild type (non-atherosclerotic mice), will demonstrate increased lipid deposition, increased cross-sectional area, and increased expression levels of collagen genes (Col1a1 and Col3a1), a growth factor gene (TGF-β), and an indicator of mast cell presence (Cpa3).
To test these hypotheses, ApoE-KO and control mice were fed a regular or high fat diet and sacrificed at different time points: 0, 15, and 30 weeks. The morphological properties were examined on H&E stained Achilles tendon sections while the lipid content was analyzed with Oil Red O staining. Tendon thickening was measured by ultrasonography of patellar tendon cross-sectional area. qPCR analysis was carried out on tail tendons at 30 week time point to analyze gene expression of Cpa3, TGF-β, Col1a1, and Col3a1.
ApoE-KO mice developed xanthomatous lesions, and showed less weight gain than control mice. ApoE-KO mice showed no appreciable changes in tendon histomorphology. Compared to control mice, ApoE-KO mice had lower tendon lipid content but demonstrated an increase in tendon cross-sectional area. Col1a1 gene expression levels were decreased in ApoE-KO mice. Cpa3, TGF-β, and Col3a1 showed no differences between strains; however, Cpa3 expression was decreased in mice that were fed the high fat diet. ApoE-KO mice demonstrated significant tendon alterations, demonstrating thicker tendons with decreased collagen expression. Future work is required to determine the mechanism involved and the potential impact on tendon function.
34
Hussein, Hala. "Activité anti-athérogène des lipoprotéines de haute densité dans les maladies métaboliques". Paris 6, 2010. http://www.theses.fr/2010PA066046.
Testo completoAbstract (sommario):
L’athérosclérose est une cause majeure de mortalité dans le monde Occidental. Les lipoprotéines de basse densité (LDL) sont les principaux transporteurs de cholestérol dans le plasma. L’oxydation de LDL est une étape clé dans l’athérogénèse du fait des propriétés pro-athérogènes et pro-inflammatoires des LDL oxydées. Les lipoprotéines de haute densité (HDL) sont très hétérogènes; les sous-fractions petites et denses d’HDL3 protègent efficacement les LDL contre l’oxydation. Deux déterminants majeurs d'une telle capacité sont la rigidité de la monocouche lipidique des HDL et leur contenu en apolipoprotèine AI (apoAI). Nos données ont montré que la capacité des sous-fractions petites et denses d’HDL3 contre l’oxydation des LDL est déficiente chez les patients avec une Hypercholestérolemie Familiale (FH). Cette altération fonctionnelle d’HDL3 est associée à une composition chimique anormale aboutissant à une rigidité élevée de la monocouche lipidique et à une concentration diminuée d’apoAI. Une seule séance de LDL-aphérèse est capable de corriger largement la composition chimique et l’altération fonctionnelle d’HDL3. De plus, nos données issues de populations avec des taux bas d’HDL-cholestérol ont révélé que l'accumulation d’HDL3 avec une concentration diminuée en apoAI et une rigidité élevée de la monocouche lipidique conduit à la diminution de la capacité d’HDL à protéger les LDL de l’oxydation chez ces sujets. En conclusion, nos données suggèrent que l'augmentation sélective de la concentration de particules fonctionnelles d’HDL3 peut constituer une approche thérapeutique pour diminuer l’athérosclérose chez des sujets avec une dyslipidémie à haut risque cardiovasculaire.
35
Lind, Suzanne. "Familial hypercholesterolemia in Sweden : genetic and metabolic studies /". Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-003-6/.
Testo completo
36
Littleton, Robert M. "Plant-Based Compound Treatment of Hypercholesterolemia in the Zebrafish". University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1355501728.
Testo completo
37
Massimo, Gianmichele <1985>. "Hypertension, hypercholesterolemia, hyperaldosteronism: a genetic perspective for personalized therapy". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6473/1/PhD_Thesis_Gianmichele_Massimo.pdf.
Testo completoAbstract (sommario):
Essential, primary, or idiopathic hypertension is defined as high BP in which secondary causes such as renovascular disease, renal failure, pheochromocytoma, hyperaldosteronism, or other causes of secondary hypertension are not present. Essential hypertension accounts for 80-90% of all cases of hypertension; it is a heterogeneous disorder, with different patients having different causal factors that may lead to high BP. Life-style, diet, race, physical activity, smoke, cultural level, environmental factors, age, sex and genetic characteristics play a key role in the increasing risk.
Conversely to the essential hypertension, secondary hypertension is often associated with the presence of other pathological conditions such as dyslipidaemia, hypercholesterolemia, diabetes mellitus, obesity and primary aldosteronism. Amongst them, primary aldosteronism represents one of the most common cause of secondary hypertension, with a prevalence of 5-15% depending on the severity of blood pressure. Besides high blood pressure values, a principal feature of primary aldosteronism is the hypersecretion of mineralcorticoid hormone, aldosterone, in a manner that is fairly autonomous of the renin-angiotensin system. Primary aldosteronism is a heterogeneous pathology that may be divided essentially in two groups, idiopathic and familial form.
Despite all this knowledge, there are so many hypertensive cases that cannot be explained. These individuals apparently seem to be healthy, but they have a great risk to develop CVD. The lack of known risk factors makes difficult their classification in a scale of risk. Over the last three decades a good help has been given by the pharmacogenetics/pharmacogenomics, a new area of the traditional pharmacology that try to explain and find correlations between genetic variation, (rare variations, SNPs, mutations), and the risk to develop a particular disease.
38
Massimo, Gianmichele <1985>. "Hypertension, hypercholesterolemia, hyperaldosteronism: a genetic perspective for personalized therapy". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6473/.
Testo completoAbstract (sommario):
Essential, primary, or idiopathic hypertension is defined as high BP in which secondary causes such as renovascular disease, renal failure, pheochromocytoma, hyperaldosteronism, or other causes of secondary hypertension are not present. Essential hypertension accounts for 80-90% of all cases of hypertension; it is a heterogeneous disorder, with different patients having different causal factors that may lead to high BP. Life-style, diet, race, physical activity, smoke, cultural level, environmental factors, age, sex and genetic characteristics play a key role in the increasing risk.
Conversely to the essential hypertension, secondary hypertension is often associated with the presence of other pathological conditions such as dyslipidaemia, hypercholesterolemia, diabetes mellitus, obesity and primary aldosteronism. Amongst them, primary aldosteronism represents one of the most common cause of secondary hypertension, with a prevalence of 5-15% depending on the severity of blood pressure. Besides high blood pressure values, a principal feature of primary aldosteronism is the hypersecretion of mineralcorticoid hormone, aldosterone, in a manner that is fairly autonomous of the renin-angiotensin system. Primary aldosteronism is a heterogeneous pathology that may be divided essentially in two groups, idiopathic and familial form.
Despite all this knowledge, there are so many hypertensive cases that cannot be explained. These individuals apparently seem to be healthy, but they have a great risk to develop CVD. The lack of known risk factors makes difficult their classification in a scale of risk. Over the last three decades a good help has been given by the pharmacogenetics/pharmacogenomics, a new area of the traditional pharmacology that try to explain and find correlations between genetic variation, (rare variations, SNPs, mutations), and the risk to develop a particular disease.
39
A, Volta. "Genetics of Familial Hypercholesterolemia: new diagnostic and research approaches". Doctoral thesis, Università di Siena, 2019. http://hdl.handle.net/11365/1071514.
Testo completoAbstract (sommario):
Introduction: Familial Hypercholesterolemia (FH, OMIM #143890) is an autosomal dominant disorder of lipoprotein metabolism characterized by high plasma levels of LDL cholesterol (LDL-C) with an estimated prevalence of 1 in 250 individuals in Western Europe. Lifelong exposure to elevated plasma levels of LDL-C leads to atherosclerosis at an early age, and as such FH patients are at a 2.2 to 25.8 fold higher risk for cardiovascular disease (CVD). FH is caused by genetic mutations that affect the structure and/or function of the LDL receptor (LDLR), a cell-surface receptor that removes LDL from the circulation. Variants in LDLR, APOB, and PCSK9 have been shown to result in clinical FH. To date, FH is an underdiagnosed and undertreated disease as exemplified by the fact that less than 1% of the worldwide familial hypercholesterolemia population is detected, diagnosed or treated according to current guidelines.
Aims: The primary aim was to promote a combined clinical and genetic approach for the diagnosis of FH in order to achieve a definitive and early diagnosis in patients, allow a prompt treatment and, thus, prevent the occurrence of CVD. Since a mutation in one of the three FH main genes is found in only 60-80% of patients with a definitive clinical diagnosis, the second aim of this PhD was to exploit genetic data, derived from the use of new DNA high-throughput sequencing (HTS) technologies, to find new molecular pathways (major or modifier genes) causing the disease. In particular, the possible association of genetic variants in ABCG5/ABCG8 and STAP1 with FH-like phenotype was investigated.
Methods and Results: Through a 55 genes targeted HTS, we set out a fast and cost-effective genetic screening for patients with a clinic suspect or a definite diagnosis of FH. In the first 2 years we analysed 32 patients and we were able to make a molecular definitive FH diagnosis in 14 of them. Our HTS design allowed also to obtain information about pharmacogenetics and genetic predisposition to other forms of dyslipidemia. The application of the 12 SNPs gene score in our FH cohort confirmed, as previously shown in literature, that the high LDL-C levels in FH patients could be due to an accumulation of several common genetic variants of small effect supporting the presence of the polygenic form of FH.
Through a lipid profiles evaluation in a big cohort of clinical FH patients and a co-segregation analysis in 4 FH families, it was then demonstrated that heterozygous variants in ABCG5/ABCG8 genes do not cause monogenic FH, although it cannot be ruled out that they can have a role in the regulation of serum cholesterol levels.
Lastly, the screening of plasma lipids and B cell profile of STAP1 variant carriers coupled with in vitro co-culture experiments allowed to demonstrate that variants in STAP1 are not associated with elevated LDL cholesterol in FH patients. Thus, in contrast to the previous literature findings, STAP1 cannot be considered the fourth FH gene.
Conclusions: This PhD thesis provides a large view on familial hypercholesterolemia, a disease with an ever higher estimated worldwide prevalence, and remarks the importance and feasibility of an
early diagnosis supported by a cost-effective genetics diagnosis approach to manage and prevent CVD. Indeed, genetics can definitely help to improve diagnosis efficiency and to quickly identify new patients within the families. Moreover, research of new genetic FH causes and the identification of novel molecular pathways causing the disease may be the groundwork to the development of novel and ever more safety and effective lipid lowering drugs.
40
Hassan, Awatef Mahdi. "Synthetic and biosynthetic studies on squalestatin". Thesis, University of Bristol, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388330.
Testo completo
41
Bourbon, Mafalda. "Characterization of molecular defects in Portuguese patients with familial hypercholesterolemia". Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423261.
Testo completo
42
Allard, Matthew. "Phenotypic characterization and cardiovascular outcomes of patients with familial hypercholesterolemia". Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/45312.
Testo completoAbstract (sommario):
Background: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder caused by mutations in the low-density lipoprotein (LDL) receptor, apolipoprotein B-100 gene, or proprotein convertase subtilisin/kexin type 9, resulting in very high blood cholesterol levels and premature cardiovascular disease (CVD).
Hypotheses/ Objectives:
1. FH patients who have developed CVD differ from those free of CVD by specific risk factors.
2. The specific risk factors differ in FH patients who develop CVD early and those resistant to CVD
3. These risk factors risk factors differ between men and women.
4. These risk factors differ between ethnic groups.
Methods: A retrospective chart review of patients in the Prevention Clinic was carried out to find individuals with “definite” FH according to the Dutch Lipid Clinic Network Criteria (DLCNC) and to determine which patients developed CVD. Cox proportional hazard regression analysis was used to assess the association of risk factors to hard cardiovascular outcomes in univariate and multivariate analyses.
Results: A total of 446 patients were identified as having “definite” FH based upon the DLCNC with 116 (26%) patients having hard evidence of CVD. Male sex, smoking, family history of premature CVD, diabetes mellitus, low HDL-C and high Lp(a) proved to be significant, independent risk factors for CVD in the entire FH cohort. The same risk factors remained significant when comparing FH patients susceptible to CVD to those resistant to CVD. Of note, LDL-C and hypertension were not important risk factors for CVD in this cohort. In men, family history, diabetes and low levels of HDL-C were significant risk factors for CVD while in women smoking, diabetes mellitus, low levels of HDL-C and high Lp(a) were significant risk factors for CVD. There were minimal detectable differences in risk factors between ethnicities.
Conclusion: In our ethnically diverse cohort the significant risk factors for CVD in decreasing order of importance were, male sex, diabetes, high Lp(a), smoking, family history of pre-mature CVD, and low HDL-C in both the entire group as well as in the most susceptible subgroup. Men and women differed in the impact of the risk factors on the presence of CVD.
43
Mansfield, Darren James. "Synthetic approaches towards Squalestatin 1 : a potent anti-hypercholesterolemic agent". Thesis, University of Exeter, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393292.
Testo completo
44
Net, J. B. van der. "Towards genetic prediction of coronary heart disease in familial hypercholesterolemia". [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2009. http://hdl.handle.net/1765/14566.
Testo completo
45
Subang, Maria Cristina. "The effect of lovestatin on hypercholesterolemia in experimental chronic renal failure /". Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=68259.
Testo completoAbstract (sommario):
Hypercholesterolemia, a major risk factor for atherosclerosis, is present in many patients with chronic renal failure (CRF). The present study was carried out in order to determine the mechanisms which underlie this increase in serum cholesterol levels and to test the feasibility of using lovastatin, a HMG-CoA reductase inhibitor in its treatment.A mouse model of surgically-induced CRF was employed in the experiments. Five weeks after the onset of renal failure, the mice were characterized with regard to various biochemical and hematological parameters. At this time, treatment with lovastatin was initiated. The drug (50, 100 and 200 mg/kg BW/day) was incorporated in powdered diet and was given fresh daily for four weeks. Upon sacrifice, blood was collected for the estimation of blood urea nitrogen and serum lipids and livers were excised for the measurement of hepatic HMG-CoA reductase activity.
The mice exhibited the major manifestations of CRF--retention of nitrogenous wastes, elevated levels of alkaline phosphatase, suggesting the presence of bone disease, and severe anemia. CRF mice also had elevated serum total cholesterol levels with a concomitant, but not significantly correlated, increase in hepatic HMG-CoA reductase activity. Furthermore, their serum lipoprotein profiles were abnormal. Treatment with lovastatin resulted in a dose-dependent reduction in serum total cholesterol levels and correction of the serum lipoprotein profile. However, hepatic HMG-CoA reductase activity was unchanged.
These results indicate that the hypercholesterolemia observed in CRF mice is probably due to an increase in de novo synthesis of cholesterol in both the liver and extranepatic tissues. Lovastatin may decrease serum total cholesterol levels in CRF mice by inhibiting peripheral, rather than hepatic, HMG-CoA reductase activity.
46
Rodríguez, Borjabad Cèlia. "Familial Hypercholesterolemia in children. From detection and characterization to lifestyle changes". Doctoral thesis, Universitat Rovira i Virgili, 2021. http://hdl.handle.net/10803/672773.
Testo completoAbstract (sommario):
La Hipercolesterolèmia Familiar (HF) és una malaltia autosòmica dominant que cursa amb nivells elevats de
lipoproteïnes de baixa densitat (LDL) des del naixement. Aquesta malaltia sovint està infradiagnostica e infratractada.
La infantesa és un període òptim per la detecció i per començar amb el tractament (canvis d’estil de vida (CEV) i en
alguns casos, estatines). Si aquests nens són detectats i tractats de forma precoç, s’ha observat que milloren el seu
pronòstic.
Per aquest motiu, la present tesi doctoral té com objectiu millorar la detecció, el diagnòstic i el tractament dels nens
amb HF. Aquest objectiu general s’aconsegueix mitjançant tres accions: 1. Establint una estratègia de detecció precoç
per detectar nens amb HF; 2. Explorant nous biomarcadors i analitzant amb més profunditat el perfil de lipoproteïnes
per ressonància magnètica nuclear (RMN); i 3. Implementant un tractament primerenc basat en activitats educatives
destinades a establir CEV.
Respecte al objectiu 1, gràcies a estratègies de cribratge actiu basats en la cascada directa e indirecta, amb l’ajuda
dels pediatres dels centres d’atenció primària, s’han detectat 87 nens i 41 familiars amb HF en dos anys. Respecte al
objectiu 2, hem observat que els nens amb HF presenten més IDOL i PCSK9, així com un major nombre de partícules
LDL petites (les més aterogèniques).La Hipercolesterolemia Familiar (HF) es una enfermedad autosómica dominante que cursa con niveles elevados de lipoproteínas de baja densidad (LDL) desde el nacimiento. Esta enfermedad a menudo está infradiagnosticado e infratratada. La infancia es un periodo óptimo para la detección y para comenzar con el tratamiento (cambios de estilo de vida (CEV) y en algunos casos, estatinas). Si estos niños son detectados y tratados de forma precoz, se ha observado que mejoran su pronóstico. Por este motivo, la presente tesis doctoral tiene como objetivo mejorar la detección, el diagnóstico y el tratamiento de los niños con HF. Este objetivo general se consigue mediante tres acciones: 1. Estableciendo una estrategia de detección precoz para detectar niños con HF; 2. Explorando nuevos biomarcadores y analizando con más profundidad el perfil de lipoproteínas por resonancia magnética nuclear (RMN); y 3. Implementando un tratamiento temprano basado en actividades educativas destinadas a establecer CEV. Respecto al objetivo 1, gracias a estrategias de cribado activo basados en la cascada directa e indirecta, con la ayuda de los pediatras de los centros de atención primaria, se han detectado 87 niños y 41 familiares con HF en dos años. Respecto al objetivo 2, hemos observado que los niños con HF presentan más IDOL y PCSK9, así como un mayor número de partículas LDL pequeñas (las más aterogénicas).
Familial hypercholesterolemia (FH) is an autosomal dominant disease with high levels of low-density lipoprotein (LDL) from birth. This disease is usually underdiagnosed and undertreated. Childhood is an optimal time for detection and initiation of treatment (lifestyle changes (LSC), and in some cases, statins). If these children are found and treated early, they have been shown to improve their prognosis. For this reason, the present doctoral thesis aims to improve the detection, diagnosis and treatment of children with FH. This general objective is achieved through three actions: 1. Establish an early detection strategy to detect children with FH; 2. Explore new biomarkers and analyse in greater depth the lipoprotein profile assessed by nuclear magnetic resonance (NMR); and 3. Implement early treatment based on educational activities aimed at establishing LSC. With respect to Objective 1, thanks to active screening strategies based on direct and indirect cascade, with the help of pediatricians from primary care centers, 87 children and 41 relatives with FH have been detected in two years. Regarding target 2, we observed that children with FH present more IDOL and PCSK9, as well as a greater number of small LDL particles (the most atherogenic). And finally, to answer objective 3, we study how diet affects the entire lipid and lipoprotein profile. We have observed that although elevated LDL levels in children with FH are genetically determined, LSC are capable of reducing their values.
47
Papadatou, Aspasia. "A controlled trial of the effectiveness of a brief psychological intervention in patients with high cholesterol levels". Thesis, University of Hertfordshire, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366029.
Testo completoAbstract (sommario):
Most research on hypercholesterolemia concerns the association of cholesterol to stress, with very few references to psychotherapeutic interventions, which are on small and motivated samples. Especially in Greece, no research has been done either on the association of cholesterol to psychological factors or the treatment of cholesterol by psychological interventions. The present study examined the effectiveness of a brief psychological intervention in decreasing high or borderline cholesterol levels. Fifty-eight hypercholesterolemic individuals were recruited for the study. This sample was a part of a group of 6,000 Athenian adults used in a long-term prospective study of cardiovascular diseases and their risk factors. Participants were partially randomised for age, sex and cholesterol into an intervention and a control group. A brief group psychological intervention was used which focused on the realisation of sources of stress and the expression of "unacceptable" thoughts and feelings. The theoretical background was psychodynamic and systemic. Intervention groups met weekly for 1 /2 hour sessions, while the control groups were invited to come to the hospital once a month for the first 3 months. The treatment outcome was assessed using blood tests of cholesterol, high density lipoproteines (HDL), low density lipoproteines (LDL), psychological tests and a questionnaire evaluating the group intervention. Participants were followed up for 1 year and were assessed at 3- month, 6-month and 1-year intervals. A statistically significant difference was found in the intervention group between the first and the second measurements of cholesterol, HDL and LDL. Also, the intervention group was found to have significantly greater decrease in cholesterol and LDL than the control group when the change scores between the initial and first follow-up measurements were compared. Significant changes were found in cholesterol, HDL and LDL in the third follow-up in the control group, which is difficult to vii explain since no association was found with any psychological or lifestyle parameters examined. No significant differences between the intervention and the control group were found on the psychological measures used in the study. However, correlations were found between decrease in cholesterol at the 1" follow-up and patients' satisfaction with the group process. The group process was analysed as well as case studies of two group members who responded well to the intervention and two who did not. These analyses suggested that participants were confronting a struggle between strong moral, social and familial obligations and their own attitudes towards life, which created strong feelings of guilt, anger and tension. Their unfamiliarity with psychotherapy and their motivation to obtain symptom relief seemed to influence the outcome of the intervention. A combination of health education and brief group psychotherapy is suggested. However, further evidence is required to support the effectiveness of brief psychological intervention in the decrease in cholesterol as well as the finding of the significant decrease in cholesterol in the control group at the 1- year follow-up.
48
Fernández, Castillejo Sara. "Effects of phenol-enriched virgin olive oils on HDL functionality in hypercholesterolemic subjects". Doctoral thesis, Universitat Rovira i Virgili, 2017. http://hdl.handle.net/10803/450869.
Testo completoAbstract (sommario):
Els nivells de lipoproteïnes de baixa densitat (HDL) estan inversament relacionats amb la malaltia cardiovascular. No obstant, estudis d’intervenció i d’associacions genètiques assenyalen que la funcionalitat o qualitat de l’HDL és un paràmetre de major importància que la quantitat d’HDL. S’han descrit diversos efectes ateroprotectors dels compostos fenòlics (CFs) de l‘oli d’oliva verge (OOV). Conseqüentment, la síntesi d’OOV funcionals (OOVFs) enriquits amb CFs podria ser una bona estratègia per incrementar el consum de CFs sense incrementar la ingesta calòrica.
La hipòtesi del present treball és que el consum sostingut d’OOVFs enriquits amb els seus propis CFs o amb ells més CFs complementaris propis de la farigola podria modificar les propietats fisicoquímiques de l’HDL i la distribució de les subclasses d’HDL, incrementant així la funcionalitat de l’HDL en individus hipercolesterolèmics.
Dues intervencions aleatoritzades, controlades, doble cec i creuades foren realitzades dins el context de l’estudi “Virgin Olive Oil and HDL Functionality”. En la intervenció d’ingesta aguda, els participants ingeriren una dosi d’OOVFs enriquits amb els seus propis CFs a diferents concentracions (250-750 ppm de CFs). En la intervenció d’ingesta sostinguda, individus hipercolesterolèmics ingeriren OOVFs enriquits amb CFs a diferents concentracions i de diferent origen (80-500 ppm de CFs de l’oli d’oliva o combinats amb CFs de la farigola) durant tres setmanes.
Els resultats mostraren que aquests OOVFs milloren la distribució de les subclasses d’HDL i diversos ratis aterogènics, incrementen la presència d’antioxidants en HDL, exerceixen un efecte beneficiós en la família de les paraoxonases i incrementen l’eflux de colesterol, d’acord amb la quantitat i l’origen dels CFs ingerits.
Conseqüentment, aquests OOVFs podrien considerar-se nutracèutics apropiats per a augmentar la funcionalitat de l’HDL i com a una eina complementaria per al tractament d’individus hipercolesterolèmics.Los niveles de lipoproteínas de alta densidad (HDL) están inversamente relacionados con la enfermedad cardiovascular. No obstante, estudios de intervención y de asociaciones genéticas señalan que la calidad funcional de la HDL es un parámetro de mayor importancia que la cantidad de HDL. Se han descrito diversos efectos ateroprotectores de los compuestos fenólicos (CFs) del aceite de oliva virgen (AOV). Por consiguiente, la síntesis de AOV funcionales (AOVFs) enriquecidos con CFs podría ser una buena estrategia para incrementar el consumo de CFs sin incrementar la ingesta calórica. La hipótesis del presente trabajo es que el consumo sostenido de AOVFs enriquecidos con sus propios CFs o con ellos más CFs complementarios propios del tomillo podría modificar las propiedades fisicoquímicas de la HDL y la distribución de las subclases de HDL, incrementando así la funcionalidad de la HDL en sujetos hipercolesterolémicos. Dos intervenciones aleatorizadas, controladas, doble ciego y cruzadas fueron realizadas en el contexto del estudio “Virgin Olive Oil and HDL Functionality”. En la intervención de ingesta aguda, los participantes ingirieron una dosis de AOVFs enriquecidos con sus propios CFs a diferentes concentraciones (250-750 ppm de CFs). En la intervención de ingesta sostenida, sujetos hipercolesterolémicos ingirieron AOVFs enriquecidos con CFs a diferentes concentraciones y de diferente origen (80-500 ppm de CFs del aceite de oliva o combinados con CFs del tomillo) durante tres semanas. Los resultados mostraron que estos AOVFs mejoran la distribución de las subclases de HDL y varios ratios aterogénicos, incrementan la presencia de antioxidantes en HDL, ejercen un efecto beneficioso en la familia de las paraoxonasas e incrementan el eflujo de colesterol, de acuerdo con la cantidad y el origen de los CFs ingeridos. Consecuentemente, estos AOVFs podrían considerarse nutracéuticos apropiados para acrecentar la funcionalidad de la HDL y como una herramienta complementaria para el tratamiento de sujetos hipercolesterolémicos.
High-density lipoprotein (HDL) cholesterol levels are inversely related to cardiovascular disease development. However, data from gene association and intervention studies lead to consider the functional quality of HDL as a more important parameter than the quantity of HDL. Phenolic compounds (PCs) from virgin olive oil (VOO) have been reported to hold atheroprotective functions. Therefore, the tailoring of functional VOOs (FVOO) enriched with PCs has been postulated as an interesting strategy to increase the daily PCs intake without increasing the caloric intake. The aim of the present thesis is that the sustained intake of FVOOs enriched with its own PCs or with them plus complementary ones from thyme may modify the physicochemical properties of HDL particles, and may promote changes in HDL subclasses distribution leading to the consequent enhancement of HDL functionality in hypercholesterolemic subjects. Two randomized, controlled, double-blind, and crossover interventions were conducted within the frame of the “Virgin Olive Oil and HDL Functionality” study. In an acute-intake intervention, participants ingested a single dose of FVOOs enriched with their own PCs but differing in the phenolic content (250-750 ppm of PCs). In a sustained-intake intervention, hypercholesterolemic participants ingested VOOs differing in PCs source and content (80-500 ppm of PCs from olive oil or combined with those from thyme) for three weeks. The results revealed that these FVOOs improve HDL subclasses profile and their associated atherogenic ratios, increase antioxidants content in HDL, exert a beneficial impact on paraoxonases family, and increase cholesterol efflux, according to PCs content and source in the FVOOs tested. Therefore, the tailoring of FVOOs could be a good nutraceutical to enhance the functionality of HDL and a complementary tool for the management of hypercholesterolemic individuals.
49
Black, Melinda Lori. "Cholesterol lowering effects of bovine serum immunoglobulin in human participants with mild hypercholesterolemia". Texas A&M University, 2005. http://hdl.handle.net/1969.1/4153.
Testo completoAbstract (sommario):
Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD).
Interestingly, the consumption of dairy products, namely milk, has been shown to lower
cholesterol. The mechanism of action surrounding this observation has been attributed
to the protein fraction of milk. While there have been many studies evaluating the
effects of dietary protein sources on cholesterol concentrations, few studies have
evaluated specific animal protein components and no human clinical studies regarding
the effects of animal plasma protein fractions on cholesterol metabolism have been
conducted. This study examined the effect of an oral serum bovine immunoglobulin
protein fraction (bIg) derived from US Department of Agriculture approved beef (aged <
30 months) on lipid indices in hypercholesterolemic humans.
Participants included men and women (aged 25 â 70 years) with mild
hypercholesterolemia (5.44-6.99 mmol/L) who were not receiving cholesterol-lowering
medication. Treatment consisted of the randomized, double blind, parallel group,
placebo-controlled administration of 5 grams (g) bIg daily for 6 weeks (W) in 52
participants (n = 26 each in treatment and control groups). Mean (ñ SD) baseline
treatment and placebo total cholesterol (TC) was 6.33 ñ 0.1 mmol/L and 6.16 ñ 0.1
mmol/L respectively. A repeated-measures multivariate analysis of covariance (MANCOVA) covaried for change in total energy and alcohol intake, and a Tukey posthoc
examination of the data showed that the bIg-treated group demonstrated a
significant reduction in TC at 3-week (W) (5.98 ñ 0.5 mmol/L; P < 0.05) and 6-week (W)
(5.97 ñ 0.7 mmol/L; P > 0.05) intervals compared to baseline. The 6W concentration
was significantly lower than the placebo group (P < 0.05). Additionally, study findings
displayed no significant changes in the placebo group or in any other lipid indexes or
markers associated with hepatorenal or cardiovascular health. Consumption of bIg
appears to lower major lipid indexes associated with CVD.
50
St-Onge, Marie-Pierre. "Effect of kefir supplementation on blood lipid parameters in free-living hypercholesterolemic men". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0024/MQ50885.pdf.
Testo completo