HDL scavenger receptor class B type I and platelet function

Purpose of review HDL cholesterol levels have been inversely correlated with thrombosis and HDL has been shown to mediate various antithrombotic effects. However, molecular mechanisms underlying the suppressing effect of HDL on platelet reactivity are not completely understood. The present review summarizes the recent advancements in understanding the role played by scavenger receptor class B type I (SR-BI) - an HDL receptor - in modulating platelet function and mediating platelet-HDL interactions. Recent findings SR-BI is expressed on platelet surface and platelets from SR-BI knockout animals are characterized by increased free-to-total cholesterol ratio, abnormal morphology, increased reactivity to strong platelets agonists, enhanced adherence to immobilized fibrinogen, and a propensity to form arterial thrombi. Crossover incubation experiments and a bone marrow transplantation approach reveal increased wild-type platelet reactivity in plasma from SR-BI-/- mice and normal or decreased SR-BI-deficient platelet reactivity in wild-type plasma. A similar functional platelet phenotype has been observed in human carriers of an SR-BI genetic variant. SR-BI ligands interfere with HDL binding to murine platelets and impede the agonist-induced platelet activation as effectively as native HDL. The inhibitory effects of native HDL, moderately oxidized HDL, and SR-BI ligands are abolished in SR-BI-deficient platelets but not in CD36-deficient platelets. Summary SR-BI exerts an indirect influence on platelet reactivity via maintaining normal plasma cholesterol homeostasis. In addition, SR-BI is a functional receptor for native and moderately oxidized HDL on platelets that generates an inhibitory signal for platelet activation.