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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1749-1750. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal 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 Gawaz, M. Search for Related Content PubMed Articles by Gawaz, M. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Next Article  HEMOSTASIS Comment on Valiyaveettil et al, page 1962 Scavenger receptors: targets for antiplatelet therapies? Meinrad Gawaz UNIVERSITÁT TÜBINGEN Scavenger receptors are increasingly recognized as playing a critical role in atherothrombosis.1 A new study presented by Valiyaveettil and colleagues in this issue of Blood demonstrates that oxidatively modified high-density lipoprotein (OxHDL) exhibits potent antiplatelet activity via the platelet scavenger receptor B type I (SR-BI). Platelets play a critical role in thrombotic diseases such as myocardial infarction or ischemic stroke. Beyond their role in thrombosis, platelets are the major trigger in boosting atherosclerosis.2 In patients with hypercholesterolemia, platelets are hyperreactive, indicating that circulating lipoproteins in blood influence platelet properties. Lipid-lowering drugs result in a reduction of platelet reactivity in these patients. Low-density (LDL), very low density (VLDL), and especially oxidized low-density lipoprotein (OxLDL), which all contain apoprotein B-100, enhance platelet activation, whereas high-density lipoprotein (HDL) has known antiplatelet effects.3 Lipoproteins bind to the platelet surface and are internalized via specific scavenger receptors. A variety of scavenger receptors have been detected on platelets, including CD36, SR-BI, and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1).4,5 OxLDL preferentially binds to CD36 and LOX-1, and activates platelets via these scavenger receptors. SR-BI has been recognized as a receptor primarily for HDL, an interaction that exerts antiplatelet activity. Thus, platelet-derived scavenger receptors may play a crucial role in thrombosis and atheroprogression. Valiyaveettil and colleagues have now identified an important mechanism allowing HDL to attenuate platelet activation. The authors' idea was based on previous findings from others indicating that HDL inhibits platelet function and that reduced levels of the HDL-binding scavenger receptor SR-BI are associated with increased platelet aggregation.6 In their unique work, Valiyaveettil and coworkers convincingly show that oxidized, but not native, HDL inhibits agonist-induced platelet activation. The inhibitory potential of OxHDL was dependent on the agonist used to activate platelets in vitro. Whereas adenosine diphosphate (ADP)– or thrombin-induced platelet activation was substantially reduced, collagen-dependent platelet aggregation was only marginally attenuated. In further studies with knock-out mice, the authors identified SR-BI as the platelet scavenger receptor that mediates the antiplatelet activity of OxHDL. Interestingly, the antiplatelet effect of OxHDL/SR-BI communication was independent of the eNOS/Akt pathway, known to play a role in HDL/SR-BI–induced eNOS activation in endothelial cells. Although the work by Valiyaveettil and colleagues implicated OxHDL as an antithrombotic strategy, data validating their findings (eg, in mouse models of thrombosis) are lacking so far. In summary, OxHDL, but not native HDL, has potent antiplatelet effects via platelet scavenger receptor SR-BI. This is a novel and intriguing finding that broadens our knowledge of how platelet-mediated hemostasis and thrombosis are regulated, especially in patients with hypercholesterolemia. The authors' findings open a new research area focusing on platelet scavenger receptors as promising antiplatelet targets. Understanding the (patho)physiologic role of platelet scavenger receptors (see figure) may not only be of interest to scientists in the field of antithrombotic research. Because platelets are the major trigger of atherosclerosis, targeting platelet scavenger receptors may offer a promising strategy to treat and attenuate atheroprogression. View larger version (51K): [in this window] [in a new window]   Hypothelial role of OxHDL/CD36 and OxHDL/SR-BI interaction in regulation of platelet function.   Footnotes Conflict-of-interest disclosure: The author declares no competing financial interests. REFERENCES Podrez EA, Byzova TV, Febbraio M, et al. Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype. Nat Med 2007; 13:1086–1095.[CrossRef][Medline] [Order article via Infotrieve] Massberg S, Brand K, Gruner S, et al. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med 2002; 196:887–896.[Abstract/Free Full Text] Surya II and Akkerman JW. The influence of lipoproteins on blood platelets. Am Heart J 1993; 125:272–275.[CrossRef][Medline] [Order article via Infotrieve] Chen M, Kakutani M, Naruko T, et al. Activation-dependent surface expression of LOX-1 in human platelets. Biochem Biophys Res Commun 2001; 282:153–158.[CrossRef][Medline] [Order article via Infotrieve] Imachi H, Murao K, Cao W, et al. Expression of human scavenger receptor B1 on and in human platelets. Arterioscler Thromb Vasc Biol 5 1, 2003; 23:898–904.[Abstract/Free Full Text] Imachi H, Murao K, Cao W, et al. Expression of human scavenger receptor B1 on and in human platelets. Arterioscler Thromb Vasc Biol 2003; 23:898–890.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI Manojkumar Valiyaveettil, Niladri Kar, Mohammad Z. Ashraf, Tatiana V. Byzova, Maria Febbraio, and Eugene A. Podrez Blood 2008 111: 1962-1971. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal 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 Gawaz, M. Search for Related Content PubMed Articles by Gawaz, M. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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