Periadventitial adipose tissue impairs coronary endothelial function via PKC-β-dependent phosphorylation of nitric oxide synthase

Gregory A. Payne, H. Glenn Bohlen, Ü Deniz Dincer, Léna Borbouse, Johnathan D. Tune

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Endogenous periadventitial adipose-derived factors have been shown to contribute to coronary vascular regulation by impairing endothelial function through a direct inhibition of endothelial nitric oxide synthase (eNOS). However, our understanding of the underlying mechanisms remains uncertain. Accordingly, this study was designed to test the hypothesis that periadventitial adipose tissue releases agents that attenuate coronary endothelial nitric oxide production via a protein kinase C (PKC)-β-dependent mechanism. Isometric tension studies were conducted on isolated canine circumflex coronary arteries with and without natural amounts of periadventitial adipose tissue. Adipose tissue significantly diminished coronary endothelial-dependent vasodilation and nitric oxide production in response to bradykinin and acetylcholine. The selective inhibition of endothelial PKC-β with ruboxistaurin (1 μM) abolished the adipose-induced impairment of bradykinin-mediated coronary vasodilation and the endothelial production of nitric oxide. Western blot analysis revealed a significant increase in eNOS phosphorylation at the inhibitory residue Thr495 in arteries exposed to periadventitial adipose tissue. This site-specific phosphorylation of eNOS was prevented by the inhibition of PKC-β. These data demonstrate that periadventitial adipose-derived factors impair coronary endothelial nitric oxide production via a PKC-β-dependent, site-specific phosphorylation of eNOS at Thr 495.

Original languageEnglish (US)
Pages (from-to)H460-H465
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume297
Issue number1
DOIs
StatePublished - Jul 1 2009

Keywords

  • Adipokine
  • Coronary circulation
  • Endothelial nitric oxide synthase
  • Protein kinase C-β

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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