Dysfunction of endothelium and overexpression of leukocyte adhesion molecule CD62L in hyperlipidemic rats

摘要

Leukocyte activation is an early manifestation of atherosclerosis in experimental models. To investigate the molecular events in blood cells leading to atherosclerosis, hyperlipidemia was induced in rats with a fat-rich diet. The hyperlipidemic animals exhibited an elevation of total cholesterol and triacylglycerol, endothelial dysfunction that resulted from a loss of nitric oxide and prostacyclin, as well as the overproduction of thromboxane A2 from activated platelets and overexpression of CD36 in endothelium. CD62L was identified in a suppression subtractive hybridization (SSH) performed to generate a profile of overexpressed genes in the blood cells of high-fat diet rats. This finding was subsequently confirmed by RT-PCR and Northern and Western blots, suggesting that the expression of CD62L is affected by dietary fat manipulation. The results of this study indicate that dietary fat may modulate inflammation, provide a point of therapeutic intervention and a pathophysiological mechanism for atherosclerosis.