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(Circulation Research. 2006;98:1352.)
© 2006 American Heart Association, Inc.

Review

Endothelial and Antithrombotic Actions of HDL

Chieko Mineo, Hiroshi Deguchi, John H. Griffin, Philip W. Shaul

From the Division of Pulmonary and Vascular Biology (C.M., P.W.S.), Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas; and Department of Molecular and Experimental Medicine (H.D., J.H.G.), The Scripps Research Institute, La Jolla, Calif.

Correspondence to Philip W. Shaul, Division of Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390-9063. E-mail philip.shaul{at}utsouthwestern.edu

This Review is part of a thematic series on New Pathways in HDL Metabolism, which includes the following articles:

Antiinflammatory Properties of HDL

Genetics of Variation in HDL Cholesterol in Humans and Mice  New Insights Into the Regulation of HDL

Metabolism and Reverse Cholesterol Transport

Endothelial and Antithrombotic Actions of HDL
Daniel Rader Guest Editor

It is well recognized that high-density lipoprotein (HDL)-cholesterol is antiatherogenic and serves a role in mediating cholesterol efflux from cells. However, HDL has multiple additional endothelial and antithrombotic actions that may also afford cardiovascular protection. HDL promotes the production of the atheroprotective signaling molecule nitric oxide (NO) by upregulating endothelial NO synthase (eNOS) expression, by maintaining the lipid environment in caveolae where eNOS is colocalized with partner signaling molecules, and by stimulating eNOS as a result of kinase cascade activation by the high-affinity HDL receptor scavenger receptor class B type I (SR-BI). HDL also protects endothelial cells from apoptosis and promotes their growth and their migration via SR-BI–initiated signaling. As importantly, there is evidence of a variety of mechanisms by which HDL is antithrombotic and thereby protective against arterial and venous thrombosis, including through the activation of prostacyclin synthesis. The antithrombotic properties may also be related to the abilities of HDL to attenuate the expression of tissue factor and selectins, to downregulate thrombin generation via the protein C pathway, and to directly and indirectly blunt platelet activation. Thus, in addition to its cholesterol-transporting properties, HDL favorably regulates endothelial cell phenotype and reduces the risk of thrombosis. With further investigation and resulting greater depth of understanding, these mechanisms may be harnessed to provide new prophylactic and therapeutic strategies to combat atherosclerosis and thrombotic disorders.

Key Words: atherosclerosis • endothelial nitric oxide synthase • endothelium • HDL • nitric oxide • prostacyclin • protein C • thrombin • thrombosis

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