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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1962-1971. Prepublished online as a Blood First Edition Paper on November 9, 2007; DOI 10.1182/blood-2007-08-107813. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-08-107813v1 111/4/1962    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Valiyaveettil, M. Articles by Podrez, E. A. Search for Related Content PubMed PubMed Citation Articles by Valiyaveettil, M. Articles by Podrez, E. A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI Manojkumar Valiyaveettil1, Niladri Kar1, Mohammad Z. Ashraf1, Tatiana V. Byzova1, Maria Febbraio2, and Eugene A. Podrez1 1 Departments of Molecular Cardiology and 2 Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH Numerous studies have reported the presence of oxidatively modified high-density lipoprotein (OxHDL) within the intima of atheromatous plaques as well as in plasma; however, its role in the pathogenesis of thrombotic disease is not established. We now report that OxHDL, but not native HDL, is a potent inhibitor of platelet activation and aggregation induced by physiologic agonists. This antithrombotic effect was concentration and time dependent and positively correlated with the degree of lipoprotein oxidation. Oxidized lipoproteins are known ligands for scavenger receptors type B, CD36 and scavenger receptor B type I (SR-BI), both of which are expressed on platelets. Studies using murine CD36–/– or SR-BI–/– platelets demonstrated that the antithrombotic activity of OxHDL depends on platelet SR-BI but not CD36. Binding to SR-BI was required since preincubation of human and murine platelets with anti–SR-BI blocking antibody abrogated the inhibitory effect of OxHDL. Agonist-induced aggregation of platelets from endothelial nitric oxide synthase (eNOS)–/–, Akt-1–/–, and Akt-2–/– mice was inhibited by OxHDL to the same degree as platelets from wild-type (WT) mice, indicating that the OxHDL effect is mediated by a pathway different from the eNOS/Akt pathway. These novel findings suggest that contrary to the prothrombotic activity of oxidized low-density lipoprotein (OxLDL), HDL upon oxidation acquires antithrombotic activity that depends on platelet SR-BI. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Scavenger receptors: targets for antiplatelet therapies? Meinrad Gawaz Blood 2008 111: 1749-1750. [Full Text] [PDF]

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