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Regulation of eNOS in Caveolae

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Caveolins and Caveolae

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 729))

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.

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Authors and Affiliations

  1. Division of Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Chieko Mineo & Philip W. Shaul

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  1. Chieko Mineo
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  2. Philip W. Shaul
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Correspondence to Chieko Mineo .

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Editors and Affiliations

  1. Department of Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Jean-François Jasmin PhD

  2. Departments of Cancer Biology, and Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Philippe G. Frank PhD  & Michael P. Lisanti MD, PhD  & 

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Mineo, C., Shaul, P.W. (2012). Regulation of eNOS in Caveolae. In: Jasmin, JF., Frank, P.G., Lisanti, M.P. (eds) Caveolins and Caveolae. Advances in Experimental Medicine and Biology, vol 729. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1222-9_4

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