The phosphorylation state of eNOS modulates vascular reactivity and outcome of cerebral ischemia in vivo

J Clin Invest. 2007 Jul;117(7):1961-7. doi: 10.1172/JCI29877.

Abstract

NO plays critical roles in vascular function. We show that modulation of the eNOS serine 1179 (S1179) phosphorylation site affects vascular reactivity and determines stroke size in vivo. Transgenic mice expressing only a phosphomimetic (S1179D) form of eNOS show greater vascular reactivity, develop less severe strokes, and have improved cerebral blood flow in a middle cerebral artery occlusion model than mice expressing an unphosphorylatable (S1179A) form. These results provide a molecular mechanism by which multiple diverse cardiovascular risks, such as diabetes and obesity, may be centrally integrated by eNOS phosphorylation in vivo to influence blood flow and cardiovascular disease. They also demonstrate the in vivo relevance of posttranslational modification of eNOS in vascular function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alanine / genetics
  • Alanine / metabolism
  • Animals
  • Aspartic Acid / genetics
  • Aspartic Acid / metabolism
  • Brain Ischemia / enzymology*
  • Brain Ischemia / genetics
  • Brain Ischemia / pathology*
  • Cerebral Arteries / enzymology
  • Cerebral Arteries / injuries
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic
  • Male
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • Nitric Oxide Synthase Type III
  • Phosphorylation
  • Regional Blood Flow
  • Serine / genetics
  • Serine / metabolism
  • Stroke / enzymology
  • Stroke / genetics
  • Stroke / pathology

Substances

  • Aspartic Acid
  • Serine
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Alanine