[Molecular identification of LOX-1 and analysis of its pathophysiological role].
Recent progress in the study of atherosclerosis revealed that the proatherogenic property of LDL is attributable to oxidized LDL. Macrophages recruited to vascular wall phagocytose oxidized LDL and transformed into foam cells, which is a hallmark of atheroma. Endothelial cells also binds oxidized LDL and changes its phenotype to the status of "endothelial dysfunction." We successfully cloned the endothelial receptor for oxidized LDL, designated LOX-1. LOX-1-mediated action of oxidized LDL induces the decrease in NO release and the increased expression of adhesion molecules, which are typical changes in endothelial dysfunction. The expression of LOX-1 is quite inducible. Proinflammatory cytokines, etc. induce the expression of LOX-1 in vitro; and proatherogenic conditions, e.g., hypertension, hyperlipidemia, and diabetes, induce the expression of LOX-1 in vivo. This manner of expression suggests the importance of LOX-1 in pathological settings. LOX-1 binds not only oxidized LDL, but also binds apoptotic cells and activated platelets through the interaction with anionic phospholipids. This property might bridge atherosclerosis and thrombosis. A novel system to detect LOX-1 ligand in plasma detected the increased level of LOX-1 ligand in hypercholesterolemic rabbits compared with normal ones. This system might be useful to predict the status of endothelial function and the risk of ischemic heart disease.
Sawamura
Tatsuya
T
Department of Bioscience, National Cardiovascular Center Research Institute, Suita 565-8565, Japan.
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003001:Cloning, Molecular; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006801:Humans; D008024:Ligands; D008077:Lipoproteins, LDL / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D011817:Rabbits; D011973:Receptors, LDL / Q000235:genetics / Q000502:physiology; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E
D015815:Cell Adhesion Molecules; D008024:Ligands; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D009569:Nitric Oxide