Upregulation of Endothelial Receptor for Oxidized LDL (LOX-1) by Oxidized LDL and Implications in Apoptosis of Human Coronary Artery Endothelial Cells: Evidence From Use of Antisense LOX-1 mRNA and Chemical Inhibitors

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 20; no. 4; pp. 1116 - 1122
• Main Authors: Li, Dayuan, Mehta, Jawahar L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.04.2000; Hagerstown, MD Lippincott
• Subjects: Apoptosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cells, Cultured; Coronary Vessels - cytology; Coronary Vessels - metabolism; DNA Fragmentation; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Gene Expression Regulation - drug effects; Humans; In Situ Nick-End Labeling; Lipoproteins, LDL - antagonists & inhibitors; Lipoproteins, LDL - pharmacology; Medical sciences; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Receptors, LDL - genetics; Receptors, Oxidized LDL; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Scavenger Receptors, Class E; Signal Transduction; Vascular disease; Human; Lipoprotein LDL; Cell culture; Endothelial cell; Pathophysiology; Coronary artery; Atherosclerosis; Cardiovascular disease; Exploration; Receiver; Apoptosis
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.20.4.1116

ABSTRACTA 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.