Caveolin-1 regulation of endothelial nitric oxide synthase function and oxidative stress in the endothelium

Marcelo G. Bonini, Randal O. Dull, Richard D. Minshall*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Scopus citations

Abstract

Numerous cardiopulmonary, autoimmune, and inflammatory diseases, as well as cigarette smoke and dietary suppressants, induce significant oxidative stress resulting in endothelial cell dysfunction, hyperproliferation, and vasoocclusive vascular disease. Maintenance of normal endothelial cell function is thought to be mediated in part via tight control over endothelial nitric oxide synthase (eNOS) activity and coupling as regulated by the membrane-associated scaffolding protein caveolin-1 (Cav-1) and the phosphatase and tensin homolog (PTEN). This chapter summarizes the literature and highlights unanswered questions of how oxidative stress affects PTEN and Cav-1 negative regulatory functions and how unleashed eNOS enzymatic activity promotes endothelial dysfunction. Focus is given to how conversion of eNOS from a transient nitric oxide-producing enzyme to a peroxynitrite-generating system in states of oxidative stress due to environmental factors, inflammation, and mechanosensitive signaling gives rise to dysfunctional cardiovascular responses. Importantly, the noted vascular defects in absence of Cav-1 and PTEN that give rise to hyperproliferative endothelial cells and remodeled vasculature can be rescued by recoupling, inhibiting, or genetically deleting eNOS, supporting the notion that strict control of eNOS enzymatic activity and signaling is critical for maintaining vascular homeostasis.

Original languageEnglish (US)
Title of host publicationSystems Biology of Free Radicals and Antioxidants
PublisherSpringer-Verlag Berlin Heidelberg
Pages1343-1363
Number of pages21
ISBN (Electronic)9783642300189
ISBN (Print)3642300170, 9783642300172
DOIs
StatePublished - May 1 2012
Externally publishedYes

Keywords

  • Cardiovascular
  • Caveolae
  • Endothelial cell reprogramming
  • Endothelial dysfunction
  • Mechanotransduction
  • Nitric oxide
  • Peroxynitrite
  • Src kinase
  • Superoxide
  • Vascular disease

ASJC Scopus subject areas

  • Medicine(all)

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