Article ; Online: Endothelial and antithrombotic actions of HDL.
2006 Volume 98, Issue 11, Page(s) 1352–1364
Abstract: ... a role in mediating cholesterol efflux from cells. However, HDL has multiple additional endothelial and ... by which HDL is antithrombotic and thereby protective against arterial and venous thrombosis, including ... class B type I (SR-BI). HDL also protects endothelial cells from apoptosis and promotes their growth and ...
| Abstract | 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. |
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| MeSH term(s) | Animals ; Endothelium, Vascular/physiology ; Fibrinolytic Agents/metabolism ; Humans ; Lipoproteins, HDL/physiology |
| Chemical Substances | Fibrinolytic Agents ; Lipoproteins, HDL |
| Language | English |
| Publishing date | 2006-06-09 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review |
| ZDB-ID | 80100-8 |
| ISSN | 1524-4571 ; 0009-7330 ; 0931-6876 |
| ISSN (online) | 1524-4571 |
| ISSN | 0009-7330 ; 0931-6876 |
| DOI | 10.1161/01.RES.0000225982.01988.93 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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