2. Academic Validation
  3. The phosphorylation state of eNOS modulates vascular reactivity and outcome of cerebral ischemia in vivo

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.
Dmitriy N Atochin 1,  Annie Wang,  Victor W T Liu,  Jeffrey D Critchlow,  Ana Paula V Dantas,  Robin Looft-Wilson,  Takahisa Murata,  Salvatore Salomone,  Hwa Kyoung Shin,  Cenk Ayata,  Michael A Moskowitz,  Thomas Michel,  William C Sessa,  Paul L Huang
Affiliations

Affiliation

  • 1 Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, MA 02129, USA.
PMID: 17557122 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.

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