Statins modulate oxidized low-density lipoprotein-mediated adhesion molecule expression in human coronary artery endothelial cells: role of LOX-1

被引:154
作者
Li, DY
Chen, HJ
Romeo, F
Sawamura, T
Saldeen, T
Mehta, JL
机构
[1] Univ Arkansas Med Sci, Dept Internal Med, Little Rock, AR 72205 USA
[2] Univ Arkansas Med Sci, Dept Physiol, Little Rock, AR 72205 USA
[3] Univ Arkansas Med Sci, Dept Biophys, Little Rock, AR 72205 USA
[4] Cent Arkansas Vet Hlth Care Syst, Little Rock, AR USA
[5] Univ Roma Tor Vergata, Dept Cardiol, Rome, Italy
[6] Uppsala Univ, Dept Forens Med, Uppsala, Sweden
[7] Osaka Univ, Natl Cardiovasc Ctr, Res Inst, Dept Biosci, Osaka, Japan
关键词
D O I
10.1124/jpet.102.034959
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
LOX-1, a receptor for oxidized low-density lipoprotein (ox-LDL), plays a critical role in endothelial dysfunction 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-methylglutaryl 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 upregulated 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 μM) was more potent than the low concentration (1 μM) (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 adhesion 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.
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收藏
页码:601 / 605
页数:5
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