Copyright © 2006, European Society of Cardiology
Circulating cardiovascular disease risk factors and signaling in endothelial cell caveolae
Division of Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX, USA
* Corresponding author. Tel.: +1 214 648 2015; fax: +1 214 648 2481. Email address: philip.shaul{at}utsouthwestern.edu
Caveolae are a subset of lipid rafts that are prevalent on the plasma membrane of endothelial cells. They compartmentalize signal transduction molecules which regulate multiple endothelial functions including the production of nitric oxide (NO) by the caveolae resident enzyme endothelial NO synthase (eNOS). Recent studies have demonstrated that circulating factors known to modify cardiovascular disease risk regulate signaling in endothelial cell caveolae. In particular, high density lipoprotein (HDL) maintains the lipid environment in caveolae, thereby promoting the retention and function of eNOS in the domain, and it also causes direct activation of eNOS via scavenger receptor type BI (SR-BI)-induced kinase signaling. Estrogen binding to estrogen receptors (ER) in caveolae also activates eNOS, and this occurs through G protein and kinase activation. Discrete domains within SR-BI and ER mediating signal initiation in caveolae have been identified. Counteracting the promodulatory actions of HDL and estrogen, C-reactive protein (CRP) antagonizes eNOS through Fc
RIIB and PP2A, which dephosphorylates and inactivates the enzyme. The endothelial cell functions modified by these processes include the regulation of monocyte adhesion and endothelial cell migration. Thus, signaling events in caveolae invoked by known circulating cardiovascular disease risk factors have major impact on endothelial cell phenotypes of importance to cardiovascular health and disease.
KEYWORDS Caveolae; C-reactive protein; Endothelium; Estrogen; High density lipoprotein; Nitric oxide
Time for primary review 21 days
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