Novel functions of lectin-like oxidized LDL receptor-1 (LOX-1)

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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 : RLPs were isolated from human plasma by immunoaffinity gel containing anti-apolipoprotein A-I and anti-apolipoprotein B-100 monoclonal antibodies.Results : 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.Conclusion : 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.