Effect of hyperlipidemia on endothelial VCAM-1 expression and the protective role of fenofibrate

Abstract

The effect of hyperlipidemia and inflammation on endothelial functions was studied. The enrolled included control (basic chow), hyperlipidemia and fenofibrate-treated groups (high fat diet). The hyperlipidemia model was set up by four-week atherogenic diet, followed by a 16-week treatment in the fenofibrate-treated group (fenofibrate 40 mg/kg every day) and without treatment in the hyperlipidemia group, respectively. In the 20th week, serum lipid level and NO levels were measured, and the expression of vascular cell adhesion molecule-1 (VCAM-1) and cell adhesiveness in aortic endothelia observed by computer-aided system. Compared with the control group, hyperlipidemia rats showed lower levels of NO and increases in leukocyte accumulation on the endothelial surface, also stronger and more extensive endothelial expression of VCAM-1. In fenofibrate-treated group, the expression of VCAM-1 and leukocyte accumulation on the endothelial surface was decreased, while serum levels of NO were increased as compared with hyperlipidemia group. Hyperlipidemia can inhibit the NO activity and promote the damage of VACA-1 to aortic endothelia. Fenofibrate can effectively prevent the pathogenesis of atherosclerosis by restoring NO levels and down-regulating the VCAM-1 expression.

Amino Acid Conjugates of 2-Mercaptobenzimidazole Ameliorates High-Fat Diet-Induced Hyperlipidemia in Rats via Attenuation of HMGCR, APOB, and PCSK9

“…Studies on animal models have shown that increased LDL levels promote the expression of VCAM1 in endothelial cells, and hypercholesterolemia can cause atherosclerosis-related pathophysiological changes in the arteries. 45,46 4J and 4K have clearly demonstrated prominent inhibition of aforementioned hyperlipidemic factors indicating their strong lipid lowering effects. Moreover, these compounds also reduced liver toxicity which is normally observed with the chronic use of statins.…”

“…The species-specific antisense APOB inhibitors have been reported to reduce LDL, VLDL, and TC. , VCAM 1 is another well-recognized marker of atherosclerotic plaque vulnerability. Its overexpression has been observed over the complete course of plaque development. , VCAM 1 expression promotes the adhesion of leukocytes to the endothelial cells, accelerates the migration of adherent leukocytes along the endothelial surface, and facilitates the proliferation of smooth muscle cells. Therefore, VCAM 1 is considered a key player in the pathogenesis of atherosclerosis.…”

“…Therefore, VCAM 1 is considered a key player in the pathogenesis of atherosclerosis. Studies on animal models have shown that increased LDL levels promote the expression of VCAM 1 in endothelial cells, and hypercholesterolemia can cause atherosclerosis-related pathophysiological changes in the arteries. , …”