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

Suzanne J. A. Korporaal*, Illiana Meurs, Arnaud D. Hauer, Reeni B. Hildebrand, Menno Hoekstra, Hugo Ten Cate, Domenico Pratico, Jan-Willem N. Akkerman, Theo J. C. van Berkel, Johan Kuiper, Miranda Van Eck

*Corresponding author for this work

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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. Methods and Results-SR-BI-deficient mice were thrombocytopenic, and their platelets were abnormally large, probably because of an increased cholesterol content. The FeCl3 acute injury model to study arterial thrombosis susceptibility showed that SR-BI wild-type mice developed total arterial occlusion after 24 +/- 2 minutes. In SR-BI-deficient mice, however, the time to occlusion was reduced to 13 +/- 1 minutes (P=0.02). Correspondingly, in SR-BI-deficient mice, platelets circulated in an activated state and showed increased adherence to immobilized fibrinogen. In contrast, platelet-specific disruption of SR-BI by bone marrow transplantation in wild-type mice did not alter plasma cholesterol levels or affect platelet count, size, cholesterol content, or reactivity, suggesting that changes in plasma cholesterol levels were responsible for the altered responsiveness of platelets in SR-BI-deficient mice. Conclusion-The function of SR-BI in HDL cholesterol homeostasis and prevention of atherosclerosis is indirectly also essential for maintaining normal platelet function and prevention of thrombosis. (Arterioscler Thromb Vasc Biol. 2011;31:34-42.)
Original languageEnglish
Pages (from-to)34–42
JournalArteriosclerosis Thrombosis and Vascular Biology
Issue number1
Publication statusPublished - Jan 2011


  • arterial thrombosis
  • platelets
  • HDL
  • SR-BI

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