Extrahepatic high-density lipoprotein receptor SR-BI and ApoA-I protect against deep vein thrombosis in mice

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Abstract

Objective-Deep vein thrombosis (DVT) and pulmonary embolism are frequent causes of morbidity and mortality. The goal of our study was to determine whether plasma high-density lipoprotein (HDL), which inversely correlates with the risk of cardiovascular events, affects DVT. Methods and Results-Using a murine DVT model of inferior vena cava stenosis, we demonstrated that deficiency of the HDL receptor, scavenger receptor class B type I (SR-BI), promotes venous thrombosis. As SR-BI mice have increased plasma cholesterol levels and abnormal HDL particles, we tested SR-BI mice with an SR-BI liver transgene that normalizes both parameters. These mice also exhibited increased susceptibility to DVT, indicating a protective role of extrahepatic SR-BI. Mice lacking the major HDL apolipoprotein apoA-I or endothelial nitric oxide synthase (eNOS) (a downstream target of endothelial SR-BI signaling) also had a prothrombotic phenotype. Intravenous infusion of human apoA-I, an HDL component and SR-BI ligend, prevented DVT in wild-type but not SR-BI or eNOS mice, suggesting that its effect is mediated by SR-BI and eNOS. Intravenous apoA-I infusion abolished histamine-induced platelet-endothelial interactions, which are important for DVT initiation. Conclusion-An apoA-I (HDL)-SR-BI-eNOS axis is highly protective in DVT and may provide new targets for prophylaxis and treatment of venous thrombosis. © 2012 American Heart Association, Inc.

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Brill, A., Yesilaltay, A., De Meyer, S. F., Kisucka, J., Fuchs, T. A., Kocher, O., … Wagner, D. D. (2012). Extrahepatic high-density lipoprotein receptor SR-BI and ApoA-I protect against deep vein thrombosis in mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(8), 1841–1848. https://doi.org/10.1161/ATVBAHA.112.252130

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