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Roles of oxidized low‐density lipoprotein and its receptors in the pathogenesis of atherosclerotic diseases
Author(s) -
Kume Noriaki,
Kita Toru
Publication year - 2002
Publication title -
geriatrics and gerontology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 57
eISSN - 1447-0594
pISSN - 1444-1586
DOI - 10.1046/j.1444-1586.2002.00048.x
Subject(s) - scavenger receptor , cd36 , foam cell , receptor , ldl receptor , lipoprotein , endocytosis , inflammation , low density lipoprotein , microbiology and biotechnology , cell surface receptor , medicine , endocrinology , chemistry , biology , cholesterol
In elderly populations, atherosclerotic diseases, including ischemic heart disease and stroke, frequently impair quality of life and affect mortality. Hypercholesterolemia, especially increased plasma low‐density lipoprotein (LDL), is one of the strongest risk factors for atheroscletorotic diseases. Oxidative modification of LDL appears to convert LDL particles to more atherogenic forms. Scavenger receptor class A (SR‐A) and CD36 have been identified and well‐characerized as receptors for Ox‐LDL in macrophages. In addition to these molecules, lectin‐like oxidized LDL receptor (LOX)‐1 and scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR‐PSOX) are type II and I membrane glycoproteins, respectively, both of which can act as cell‐surface endocytosis receptors for atherogenic oxidized LDL (Ox‐LDL). LOX‐1 expression can dynamically be induced by pro‐inflammatory stimuli, and is detectable in cultured macrophages and activated vascular smooth muscle cells (VSMC), in addition to endothelial cells. LOX‐1‐dependent uptake of Ox‐LDL induces apoptosis of cultured VSMC. In vivo , endothelial cells that cover early atherosclerotic lesions, and intimal macrophages and VSMC in advanced atherosclerotic plaques dominantly express LOX‐1. LOX‐1 expressed on the cell‐surface can be cleaved in part and released as soluble molecules, suggesting the diagnostic value of soluble LOX‐1. SR‐PSOX is a newly identified receptor for Ox‐LDL, which appears to be identical to CXCL16, a novel membrane‐anchored chemokine directed to CXCR6‐positive lymphocytes. In contrast to LOX‐1, which is expressed by a variety of cell types, SR‐PSOX expression appeared relatively confined to macrophages in atherogenesis. Taken together, oxidized LDL receptors, including LOX‐1 and SR‐PSOX, may play important roles in atherogenesis and atherosclerotic plaque rupture.