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

Arterioscler Thromb Vasc Biol. 2012 Aug;32(8):1841-7. doi: 10.1161/ATVBAHA.112.252130. Epub 2012 May 31.


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.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apolipoprotein A-I / pharmacology*
  • Blood Coagulation
  • Blood Platelets / drug effects
  • Blood Platelets / physiology
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type III / physiology
  • Scavenger Receptors, Class B / physiology*
  • Venous Thrombosis / prevention & control*


  • Apolipoprotein A-I
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse