Upregulation of Endothelial Receptor for Oxidized LDL (LOX-1) by Oxidized LDL and Implications in Apoptosis of Human Coronary Artery Endothelial Cells
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- 1 April 2000
- journal article
- other
- Published by Wolters Kluwer Health in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 20 (4) , 1116-1122
- https://doi.org/10.1161/01.atv.20.4.1116
Abstract
—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-1 by oxidized low density lipoprotein (ox-LDL) and determined the role of LOX-1 in ox-LDL–induced apoptosis of cultured human coronary artery endothelial cells (HCAECs). Incubation of HCAECs with ox-LDL (40 μg/mL), but not native LDL, for 24 hours markedly increased LOX-1 expression (mRNA and protein). After 48 hours of preincubation of HCAECs with a specific antisense to LOX-1 mRNA (antisense LOX-1), ox-LDL–mediated upregulation of LOX-1 was suppressed (P<0.01). In contrast, treatment of HCAECs with sense LOX-1 had 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-1 played an important role in ox-LDL–mediated apoptosis of HCAECs because antisense LOX-1 inhibited this effect of ox-LDL. Polyinosinic acid and carrageenan, 2 different chemical inhibitors of LOX-1, also decreased ox-LDL–mediated apoptosis of HCAECs. Nuclear factor (NF)-κB was markedly activated in ox-LDL–treated HCAECs. The critical role of NF-κB activation became evident in experiments with antisense LOX-1, which abolished ox-LDL–mediated NF-κB activation. In this process, an NF-κB 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-κB activation may play an important role as a signal transduction mechanism.Keywords
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