Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI.

摘要: Numerous studies have reported the presence of oxidatively modified high-density lipoprotein (OxHDL) within intima atheromatous plaques as well in plasma; however, its role pathogenesis thrombotic disease is not established. We now report that OxHDL, but native HDL, a potent inhibitor platelet activation and aggregation induced by physiologic agonists. This antithrombotic effect was concentration time dependent positively correlated with degree oxidation. Oxidized lipoproteins are known ligands for scavenger receptors type B, CD36 receptor B I (SR-BI), both which expressed on platelets. Studies using murine CD36−/− or SR-BI−/− platelets demonstrated activity OxHDL depends SR-BI CD36. Binding to required since preincubation human anti–SR-BI blocking antibody abrogated inhibitory OxHDL. Agonist-induced from endothelial nitric oxide synthase (eNOS)−/−, Akt-1−/−, Akt-2−/− mice inhibited same wild-type (WT) mice, indicating mediated pathway different eNOS/Akt pathway. These novel findings suggest contrary prothrombotic oxidized low-density (OxLDL), HDL upon oxidation acquires SR-BI.