Increased Atherosclerosis in Mice Deficient in Perilipin1

<p>Abstract</p> <p>Background</p> <p>Perilipin1, a lipid droplet associated protein has an important role in the regulation of lipolysis and lipid storage in adipocytes. Perilipin1 is also expressed in foam cells of atheroma plaques and could therefore play a role in the accumulation of lipids in arterial wall and in the development of atherosclerosis. The aim of the study was to investigate this possible role of perilipin1 in atherogenesis.</p> <p>Methods</p> <p>Mice deficient in perilipin1 (<it>Plin1-/-) </it>were crossed with <it>Ldlr-/- </it>mice. <it>Ldlr-/- </it>and <it>Plin1-/- Ldlr-/- </it>mice received an atherogenic diet during 10 or 20 weeks. Blood pressure and plasma lipids concentrations were measured. Aortas were collected at the end of the atherogenic diet periods for quantification of atheroma lesions (<it>en face </it>method), histological and immunohistological studies</p> <p>Results</p> <p><it>Ldlr-/- </it>and <it>Plin1-/- Ldlr-/- </it>mice had comparable blood pressure and plasma lipids levels. <it>Plin1-/- Ldlr-/- </it>mice had a lower body weight and decreased adiposity. The atherosclerotic lesion area in <it>Plin1-/-Ldlr-/- </it>mice was moderately increased after 10 weeks of atherogenic diet (ns) and significantly higher after 20 weeks (p < 0.01). Histology of atheroma plaques was comparable with no sign of increased inflammation in <it>Plin1-/- Ldlr-/- </it>mice.</p> <p>Conclusion</p> <p>Perilipin1 ablation in mice results in increased atherosclerosis independently of modifications of risk factors such as raised blood pressure or plasma lipids levels. These data strongly support an atheroprotective role for perilipin1.</p

Thyroid Hormone Receptor Alpha Deletion in ApoE^–/– Mice Alters the Arterial Renin-Angiotensin System and Vascular Smooth Muscular Cell Cholesterol Metabolism

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TRα inhibits arterial renin-angiotensin system expression and prevents cholesterol accumulation in vascular smooth muscle cells

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Effet thérapeutique de l’extrait aqueux de Globularia alypum suite à une insulinotoxicité induite in vitro sur les cardiomyocytes de Rattus norvegicus. [Therapeutic effect of aqueous extract of Globularia alypum following in vitro insulin induced toxicity on Rattus norvegicus cardiomyocytes]

Introduction. L’insulino‐résistance, marquée par une réaction inflammatoire via la production de TNF‐α et par l’hyperinsulinémie compensatoire, conduit à long terme à l’installation d’une glucolipotoxicité et du diabète de type 2. Objectif. Dans cette étude, les effets d’un extrait aqueux de Globularia alypum (Ga) a été analysé in vitro, suite à un stress induit sur le cardiomyocyte de Rattus norvegicus. Matériel et Méthodes. Le stress a été induit par addition d’une dose élevée d’insuline (10 UI/ mL). Les taux de prolifération ont été déterminés par comptage et les contenus cellulaires en monoxyde d’azote (NO), en malondialdéhyde (MDA) et en catalase ont été évalués. Résultats. En présence de la dose élevée d’insuline, les cardiomyocytes ont montré une diminution de la survie cellulaire, un déséquilibre du statut redox en faveur d’une augmentation de NO et de MDA et d’une diminution d’une enzyme du système antioxydant, la catalase. Suite à l’action de l’extrait de Ga, il a été noté une amélioration du taux de prolifération cellulaire, une diminution du taux de No et de MDA ainsi qu’une augmentation de l’activité de la catalase. Conclusion. L’état de stress induit sur le cardiomyocyte par l’insulino‐résistance, mimé par la dose élevée d’insuline, entraîne des altérations physiologiques et biochimiques. Ces dernières, précurseurs de mort cellulaire par apoptose sont atténuées après addition d’un extrait de Globularia alypum, lequel pourrait constituer une cible thérapeutique en aval de l’installation du DT2

Glucotoxicity Induced Oxidative Stress and Inflammation In Vivo

Context. Brassica rapa is considered as natural source of antioxidants and is used to treat diabetes. Objective. Our study carried the impact of glucotoxicity induced in vivo and in vitro in vascular smooth muscle cells (VSMCs) in Psammomys and the therapeutic effect of Brassica rapa (AEBr). Materials and Methods. We administered a hyperglucidic diet (30% sucrose) for 9 months and a treatment for 20 days with AEBr at 100 mg/kg. VSMCs were submitted to D-Glucose (0.6%) for 48 hours and treated with AEBr (2100 μg/mL) for 24 hours. We measured, in blood metabolic parameters, the redox statues and inflammatory markers in adipose tissue. Histological study was effectuated in liver. In VSMCs, we measured markers of glucotoxicity (IRS1p Serine, AKT) inflammation (NO, MCP1, TNFα, and NF-κB) and oxidative stress (oxidants and antioxydants markers). Cell viability and apoptosis were estimated by the morphological study. Results. AEBr corrects the metabolic parameters and inflammatory and oxidative markers in blood and homogenate tissue and reduces lipid droplets in liver. It induces, in VSMCs, a significant decrease of IRS1p serine, cyt c, NO, MCP1, TNFα, NF-κB, protein, and lipid oxidation and increases cell viability, AKT, ERK1/2, catalase, and SOD activity. Conclusion. Brassica enhanced the antidiabetic, anti-inflammatory, and antioxidant defense leading to the protection of cardiovascular diseases