Regulation of eNOS in caveolae

Research output: Chapter in Book/Report/Conference proceedingChapter

55 Scopus citations

Abstract

Caveolae are a specialized subset of lipid domains 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). eNOS is one of the three isoforms of the NOS enzyme which generates NO upon the conversion of L-arginine to L-citrulline and it is regulated by multiple mechanisms. Caveolin negatively impact eNOS activity through direct interaction with the enzyme. Circulating factors known to modify cardiovascular disease risk also influence the activity of the enzyme. In particular, high density lipoprotein cholesterol (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 class B, Type I (SR-BI)-induced kinase signaling. Estrogen binding to estrogen receptors (ER) in caveolae also activates eNOS and this occurs through G protein coupling 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 FcγRIIB, which is the sole inhibitory receptor for IgG. Through their actions on eNOS, estrogen and CRP also regulate endothelial cell growth and migration. Thus, signaling events in caveolae invoked by known circulating cardiovascular disease risk factors have major impact on eNOS and endothelial cell phenotypes of importance to cardiovascular health and disease.

Original languageEnglish (US)
Title of host publicationCaveolins and Caveolae
Subtitle of host publicationRoles in Signaling and Disease Mechanisms
Pages51-62
Number of pages12
DOIs
StatePublished - Apr 20 2012

Publication series

NameAdvances in Experimental Medicine and Biology
Volume729
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Mineo, C., & Shaul, P. W. (2012). Regulation of eNOS in caveolae. In Caveolins and Caveolae: Roles in Signaling and Disease Mechanisms (pp. 51-62). (Advances in Experimental Medicine and Biology; Vol. 729). https://doi.org/10.1007/978-1-4614-1222-9_4