Scavenger receptor BI modulates platelet reactivity and thrombosis in dyslipidemia.
نویسندگان
چکیده
Hypercholesterolemia is associated with increased platelet sensitivity to agonists and a prothrombotic phenotype. Mechanisms of platelet hypersensitivity are poorly understood; however, increased platelet cholesterol levels associated with hypercholesterolemia were proposed as leading to hypersensitivity. Scavenger receptor class B type I (SR-BI) in the liver controls plasma high-density lipoprotein (HDL) levels, and SR-BI-deficient mice display a profound dyslipoproteinemia. SR-BI is also expressed on platelets, and recent studies have suggested a role for SR-BI in platelet function; however, its role in hemostasis is unknown. Our present studies demonstrated that non-bone marrow-derived SR-BI deficiency and the dyslipidemia associated with it lead to platelet hyperreactivity that was mechanistically linked to increased platelet cholesterol content. Platelet-specific deficiency of SR-BI, on the other hand, was associated with resistance to hyperreactivity induced by increased platelet cholesterol content. Intravital thrombosis studies demonstrated that platelet SR-BI deficiency protected mice from prothrombotic phenotype in 2 types of dyslipidemia associated with increased platelet cholesterol content. These novel findings demonstrate that SR-BI plays dual roles in thrombosis and may contribute to acute cardiovascular events in vivo in hypercholesterolemia.
منابع مشابه
PLATELETS AND THROMBOPOIESIS Scavenger receptor BI modulates platelet reactivity and thrombosis in dyslipidemia
Hypercholesterolemia is associated with increased platelet sensitivity to agonists and a prothrombotic phenotype. Mechanisms of platelet hypersensitivity are poorly understood; however, increased platelet cholesterol levels associated with hypercholesterolemia were proposed as leading to hypersensitivity. Scavenger receptor class B type I (SR-BI) in the liver controls plasma high-density lipopr...
متن کاملDeletion of the high-density lipoprotein receptor scavenger receptor BI in mice modulates thrombosis susceptibility and indirectly affects platelet function by elevation of plasma free cholesterol.
OBJECTIVE Scavenger receptor BI (SR-BI) is a cell surface receptor that promotes the selective uptake of cholesteryl esters from high-density lipoprotein (HDL) by the liver. In mice, SR-BI deficiency results in increased plasma HDL cholesterol levels and enhanced susceptibility to atherosclerosis. The aim of this study was to investigate the role of SR-BI deficiency on platelet function. METH...
متن کاملIntegrative Physiology and Experimental Medicine Deletion of the High-Density Lipoprotein Receptor Scavenger Receptor BI in Mice Modulates Thrombosis Susceptibility and Indirectly Affects Platelet Function by Elevation of Plasma Free Cholesterol
متن کامل
Scavenger receptors: targets for antiplatelet therapies?
P latelets 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. Lipidlowering drugs result in a reduction of pla...
متن کاملHEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI
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 antithr...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Blood
دوره 116 11 شماره
صفحات -
تاریخ انتشار 2010