期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 32, 期 8, 页码 1841-U308出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.112.252130
关键词
deep vein thrombosis; scavenger receptor class B type I; apolipoprotein A-I; high-density lipoprotein; endothelial nitric oxide synthase
资金
- National Heart, Lung, and Blood Institute of the National Institutes of Health [P01 HL066105, HL52212, R01 HL041002]
- Fond voor Wetenschappelijk Onderzoek Vlaanderen (FWO)
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. (Arterioscler Thromb Vasc Biol. 2012;32:1841-1848.)
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