Lectin-like oxidized LDL receptor-1 (LOX-1) acts as a receptor for remnant-like lipoprotein particles (RLPs) and mediates RLP-induced migration of vascular smooth muscle cells

Abstract

Objective Remnant-like lipoprotein particles (RLPs) have been implicated in atherogenesis especially by diabetic dyslipidemia; however, their receptor(s) and effects on vascular smooth muscle cells (VSMCs) remain unclear. In this study, we examined if lectin-like oxidized LDL receptor-1 (LOX-1) acts as a receptor for RLPs and its biological effects in VSMCs. Methods and results RLPs were isolated from human plasma by immunoaffinity gel containing anti-apolipoprotein A-I and anti-apolipoprotein B-100 monoclonal antibodies. DiI-labeled RLPs were taken up by CHO-K1 cells stably expressing LOX-1 but not by wild-type CHO-K1 cells. RLPs induced LOX-1 expression and cell migration in bovine VSMCs (BVSMCs), which were significantly suppressed by transfection with LOX-1 specific siRNAs. Inhibitors of metalloproteinases, epidermal growth factor (EGF) receptor tyrosine kinase, heparin-binding EGF-like growth factor (HB-EGF), p38 mitogen-activated protein kinase (p38 MAPK), MAPK kinase (MEK1) and phosphoinositide 3-kinase (PI3K) significantly blocked RLP-induced LOX-1 expression and cell migration of BVSMCs. Conclusions The present study provides direct evidence that LOX-1 is a novel receptor for RLPs in VSMCs. LOX-1-mediated uptake of RLPs may thus play important roles in atherogenesis by inducing LOX-1 expression and VSMC migration especially in the settings of postprandial hyperlipidemia, diabetes and metabolic syndrome.