Lipogenesis in arterial wall and vascular smooth muscular cells: regulation and abnormalities in insulin-resistance

Abstract

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.

Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress

“…Vascular expression of PXR mRNA has been shown previously in rat and Psammomys obesus gerbil thoracic aortic smooth muscle cells (SMC), rat, pig, and human brain capillary endothelial cells, and mouse mesenteric arteries. 11 – 18 The latter was indicated in regulating vasodilation during pregnancy via up-regulation of CYP epoxygenases. 18 Here, we show that PXR is expressed in the vasculature across species, where it co-ordinates a gene programme of Phase I and II drug-metabolizing enzymes and transporters, providing a mechanism by which the vasculature can protect itself and the underlying tissues from circulating xenobiotic and endobiotic insults.…”

Distinct regulation of stearoyl-CoA desaturase 1 gene expression by cis and trans C18:1 fatty acids in human aortic smooth muscle cells

“…VSMC also play a preponderant role in the pathogenesis of atherosclerosis by their migration and proliferation in the intima of arterial wall, where they accumulate lipids and contribute to the promotion of inflammation process (Orr et al 2010). Accumulation of lipid in VSMC is associated to either uptake of lipoproteins and fatty acids from plasma, or de novo lipogenesis with increased expression of lipogenic genes such as stearoyl-CoA desaturase (scd) (Leake and Peters 1982;Mietus-Snyder et al 1997;Portman 1970;Ricciarelli et al 2000;Davies et al 2005;Hamlat et al 2009). The stearoyl-CoA desaturase localizes in the endoplasmic reticulum and exists under two isoforms scd1 and scd5 in human (Wang et al 2005).…”

Fatty Acid Metabolism Disorder as a Factor in Atherogenesis

“…The accumulation of these lipids can significantly affect the formation and growth of an atherosclerotic plaque. This conclusion can be confirmed by the fact that atherosclerotic plaques accumulate not only cholesterol, but also a significant amount of triglycerides [16]. Furthermore, in the event when free cholesterol appears in an atherosclerotic plaque, its cells apparently use oleic acid which is predominant in the spectrum of FFA for the sake of esterification of cholesterol and its storage.…”

“…The ratio of myristoleic (C 14:1 ) FA in them constitutes 13.08 [12.09; 13.30] % to the content of myristic (C 14:0 ) acid, in contrast to the control aortas, wherein the ratio of C 14:1 is 6.86 [5.52; 7.40] % to C 14:0 (p < 0.05). The ratio of palmitoleic (C 16:1 ) FA to palmitic (C 16 Common carotid arteries of the experimental group (in spite of the absence of signs of atherosclerosis), in contrast to the control carotid arteries, also have an increased content of monounsaturated FA with respect to the corresponding saturated acids (p < 0.05). Thus, the content of C 14:1 in them is 11.45 [11.12; 11.88 The findings suggest that there is an activation of 9-desaturase, which catalyzes the formation of monounsaturated acids from saturated acids.…”