期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 20, 期 4, 页码 1116-1122出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.20.4.1116
关键词
apoptosis; endothelial cells; LOX-1; nuclear factor-kappa B; oxidized LDL
A specific lectinlike endothelial receptor for oxidized low density lipoprotein (LOX-1), distinct from the scavenger receptor in monocytes/macrophages, has been identified and cloned. In this study, we examined the regulation of LOX-I by oxidized low density Lipoprotein (ox-LDL) and determined the role of LOX-1 in ox-LDL-indnced apoptosis of cultured human coronary artery endothelial cells (HCAECs). Incubation of HCAECs with ox-LDL (40 mu g/mL), but not native LDL, for 24 hours markedly increased LOX-I expression (mRRTA and protein). After 48 hours of preincubation of HCAECs with a specific antisense to LOX-I mRNA (antisense LOX-1), ox-LDL mediated upregulation of LOX-I was suppressed (P<0.01). In contrast, treatment of HCAECs with sense LOX-I bad no effect. Ox-LDL also induced apoptosis (determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling and DNA laddering) of HCAECs in a concentration- and time-dependent fashion. LOX-I played an important role in ox-LDL-mediated apoptosis of HCAECs because antisense LOX-I inhibited this effect of ox-LDL. Polyinosinic acid and carrageenan, 2 different chemical inhibitors of LOX-I, also decreased ox-LDL-mediated apoptosis of HCAECs. Nuclear factor (NF)-kappa B was markedly activated in ox-LDL-treated HCAECs. The critical role of NF-KB activation became evident in experiments with antisense LOX-1, which abolished ox-LDL-mediated NF-kappa B activation. In this process, an NF-KB inhibitor, caffeic acid phenethyl ester, also inhibited ox-LDL-mediated apoptosis of HCAECs. These findings indicate that ox-LDL upregulates its own endothelial receptor. Ox-LDL-induced apoptosis is mediated by the action of LOX-1. In this process, NF-kappa B activation may play an important role as a signal transduction mechanism.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据