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

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

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124 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1961-1967
Number of pages7
JournalJournal of Clinical Investigation
Volume117
Issue number7
DOIs
Publication statusPublished - 2 Jul 2007
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Atochin, D. N., Wang, A., Liu, V. W. T., Critchlow, J. D., Dantas, A. P. V., Looft-Wilson, R., Murata, T., Salomone, S., Hwa, K. S., Ayata, C., Moskowitz, M. A., Michel, T., Sessa, W. C., & Huang, P. L. (2007). The phosphorylation state of eNOS modulates vascular reactivity and outcome of cerebral ischemia in vivo. Journal of Clinical Investigation, 117(7), 1961-1967. https://doi.org/10.1172/JCI29877