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BackgroundVascular smooth muscular cells (VSMC) express lipogenic genes. Therefore in situ lipogenesis could provide fatty acids for triglycerides synthesis and cholesterol esterification and contribute to lipid accumulation in arterial wall with aging and during atheroma.MethodsWe investigated expression of lipogenic genes in human and rat arterial walls, its regulation in cultured VSMC and determined if it is modified during insulin-resistance and diabetes, situations with increased risk for atheroma.ResultsZucker obese (ZO) and diabetic (ZDF) rats accumulated more triglycerides in their aortas than their respective control rats, and this triglycerides content increased with age in ZDF and control rats. However the expression in aortas of lipogenic genes, or of genes involved in fatty acids uptake, was not higher in ZDF and ZO rats and did not increase with age. Expression of lipogenesis-related genes was not increased in human arterial wall (carotid endarterectomy) of diabetic compared to non-diabetic patients. In vitro, glucose and adipogenic medium (ADM) stimulated moderately the expression and activity of lipogenesis in VSMC from control rats. LXR agonists, but not PXR agonist, stimulated also lipogenesis in VSMC but not in arterial wall in vivo. Lipogenic genes expression was lower in VSMC from ZO rats and not stimulated by glucose or ADM.ConclusionLipogenic genes are expressed in arterial wall and VSMC; this expression is stimulated (VSMC) by glucose, ADM and LXR agonists. During insulin-resistance and diabetes, this expression is not increased and resists to the actions of glucose and ADM. It is unlikely that this metabolic pathway contribute to lipid accumulation of arterial wall during insulin-resistance and diabetes and thus to the increased risk of atheroma observed in these situations.

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Thyroid hormones (TH) have several effects on the cardiovascular system. A slight decline in TH levels has harmful effects on the vascular system. The current study aimed to investigate whether a decrease in TH plasma levels was responsible for the expression of some atherosclerosis markers. Experimental hypothyroidism was induced in Psammomys obesus by administering 0.03% carbimazole in their drinking water for five months (M5). The animals were sacrificed at M5, and histopathological analysis of the thoracic aorta and thyroid gland was performed after Masson's trichrome staining. The expression of the angiotensinogen (Agt) gene and the genes implicated in cholesterol metabolism regulation in the liver and vascular smooth muscle cells (VSMCs) was determined by qRT-PCR. Finally, we assessed the in vitro proliferation rate of VSMCs derived from the aortas of the two groups of animals. Hypothyroidism was associated with increased expression of Agt in the liver and 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr) and Acyl CoA:cholesterol acyltransferase (Acat) 1 genes (cholesterol synthesis and esterification pathway) in VSMCs, with failure to increase efflux pathway genes (ATP-binding cassette subfamily G member (Abcg) 1 and 4) in these vascular cells. Moreover, reduction in TH induces aortic endothelial cell and subendothelium hypertrophy, and disorganization of the media with rupture of the elastic fiber network. All these results suggest that hypothyroidism can lead to atherosclerosis through the alteration of the physiology of VSMCs, mainly the phenotype switch and gene expression modification involved in the regulation of cholesterol metabolism.

Objective: Chronic hyperglycemia characteristic of type diabetes 2 is responsible for the accelerated atherosclerosis with increased cardiovascular risk. In this study, we will propose to analyze the effect of a long-term of glucotoxicity in vivo in Psammomys obesus by addition of sucrose to 30% for 11 months and in vitro study of adventitial fibroblasts in the presence of D-glucose 0.6% for 7 days. Materials and methods: Evaluation of plasma biochemical parameters was carried out at the initial time and at the end of experiment. At autopsy, a morphological study of the aorta was performed after fixation in aqueous Bouin and staining with Masson's trichrome. The experimental glucotoxicity is induced by incubation of fibroblasts in DMEM enriched with D-glucose at 0.6% for 7 days. The impact of glucotoxicity is assessed in the intracellular compartments through dosage of total nitrite and malondialdehyde, a product of lipid peroxidation, and thanks to a morphological assay after fixation of cells with aqueous bouin and blood staining with May Grünwald Giemsa. The evaluation of cell proliferation is accomplished by cell counting. Collagens I and III of the extracellular compartment are characterized by SDS-PAGE. Results: Animals subjected to sucrose showed hyperglycemia associated with hyperinsulinemia, dyslipidemia, hyperproteinemia, increased CPK and VLDL-LDL and decreased HDL. Histology of aortas revealed endothelial cells hypertrophy, severe disorganization of intima and media. In the presence of glucose, the proliferation of fibroblasts increases very significantly (P = 2.34 × 10

Thyroid hormone (TH) regulates gene transcription by binding to TH receptors (TRs). TRs regulate the genes of lipid metabolism and the renin-angiotensin system (RAS). We examined the effect of TRα deletion in ApoE^–/– mice (DKO mice) on the following: (i) the expression of genes controlling cholesterol metabolism and tissue (t)RAS in the liver and aorta and (ii) the expression of these genes and the regulation of cholesterol content in cultured vascular smooth muscle cells (VSMCs). TRα deletion in ApoE^–/– mice led to the repression of genes involved in the synthesis and influx of cholesterol in the liver. However, TRα deletion in the arterial wall suppressed the expression of genes involved in the esterification and excretion of cholesterol and enhanced the expression of angiotensinogen (AGT). The VSMCs of the ApoE^–/– and DKO mice increased their cholesterol content during cholesterol loading, but failed to increase the expression of ATP-binding cassette transporter A1 (ABCA1). T₃ addition partially corrected these abnormalities in the cells of the ApoE^–/– mice but not those of the DKO mice. In conclusion, TRα deletion in ApoE^–/– mice slightly increases the expression of tRAS in the aorta and aggravates the dysregulation of cholesterol content in the VSMCs.