Stains Modulate Oxidized Low-Density Lipoprotein-Mediated Adhesion Molecule Expression in Human Coronary Artery Endothelial Cells: Role of LOX-1

摘要

LOX-1, a receptor for oxidized low-density lipoprotein (ox-LDL), plays a critical role in endothelialdysfunction and atherosclerosis. LOX-1 activation also plays an important role in monocyte adhesion to endothelial cells. A number of studies show that 3-hydroxy-3-methylglutary coenzyme A reductase inhibitors (statins) reduce total LDL cholesterol and exert a cardioprotective effect. We examined the modulation of LOX-1 expression and its function by two different statins, simvastatin and atorvastatin, in human coronary artery endothelial cells (HCAECs). We observed that ox-LDL (40 mug/ml) treatment up-regulated the expression of E-and P-selectins, VCAM-1 and ICAM-1 in HCAECs. Ox-LDL mediated these effects via LOX-1, since antisense to LOX-1 mRNA decreased LOX-1 expression and subsequent adhesion molecule expression. Pretreatment of HCAECs with simvastatin or atorvastatin (1 and 10 muM) reduced ox-LDL-induced expression of LOX-1 as well as adhesion molecules (all P < 0.05). A high concentration of statins (10 muM) was more potent than the low concentration (1 muM) (P < 0.05). Both statins reduced ox-LDL-mediated activation of the redox-sensitive nuclear factor-kappaB (NF-kappaB) but not AP-1. These observations indicate that LOX-1 activation plays an important role in ox-LDL-induced expression of adheison molecules. Inhibition of expression of LOX-1 and adhesion molecules and activation of NF-kappaB may be another mechanism of beneficial effects of statins in vascular diseases.