Endothelial and antithrombotic actions of HDL

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

Research output: Contribution to journalArticle

438 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1352-1364
Number of pages13
JournalCirculation Research
Volume98
Issue number11
DOIs
StatePublished - Jun 2006

Fingerprint

HDL Lipoproteins
CD36 Antigens
Nitric Oxide Synthase
Endothelial Cells
Cholesterol
Caveolae
Selectins
Nitric Oxide Synthase Type III
Platelet Activation
Thromboplastin
Epoprostenol
Protein C
Thrombin
Venous Thrombosis
HDL Cholesterol
Atherosclerosis
Nitric Oxide
Thrombosis
Phosphotransferases
Down-Regulation

Keywords

  • Atherosclerosis
  • Endothelial nitric oxide synthase
  • Endothelium
  • HDL
  • Nitric oxide
  • Prostacyclin
  • Protein C
  • Thrombin
  • Thrombosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Endothelial and antithrombotic actions of HDL. / Mineo, Chieko; Deguchi, Hiroshi; Griffin, John H.; Shaul, Philip W.

In: Circulation Research, Vol. 98, No. 11, 06.2006, p. 1352-1364.

Research output: Contribution to journalArticle

Mineo, Chieko ; Deguchi, Hiroshi ; Griffin, John H. ; Shaul, Philip W. / Endothelial and antithrombotic actions of HDL. In: Circulation Research. 2006 ; Vol. 98, No. 11. pp. 1352-1364.
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