New oxidized LDL receptors and their functions in atherogenesis

Abstract

Oxidized low density lipoprotein (Ox-LDL) appears to play key roles in atherosclerotic progression and plaque rupture. Biological effects of Ox-LDL on vascular cells may, at least in part, be mediated by cell surface receptors for Ox-LDL. Lectin-like oxidized LDL receptor (LOX)-1 and scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) are type II and I membrane glycoprtoeins, 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 proinflammatory 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 induced 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 cellsurface can be cleaved, in part, and released as soluble molecules, suggesting the diagnostic significance of plasma soluble LOX-1 levels. SR-PSOX appeared to be identical to CXCL16, a novel membrane-anchored chemokine directed to CXCR6-positive lymphocytes, suggesting another role of SR-PSOX as T-cell chemoattractant. In contrast to LOX-1 expressed by a variety of cell types. SR-PSOX expression appeared relatively confined to macrophages in atherogenesis. Taken together, LOX-1 and SR-PSOX may play important roles in atherogenesis and athrosclerotic plaque rupture.