title: The phosphorylation state of eNOS modulates vascular reactivity and outcome of cerebral ischemia in vivo.
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.
authors.affiliation: Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, MA 02129, USA.
authors.forename: Dmitriy N
authors.initials: DN
authors.lastname: Atochin
authors.forename: Annie
authors.initials: A
authors.lastname: Wang
authors.forename: Victor W T
authors.initials: VW
authors.lastname: Liu
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Critchlow
authors.forename: Ana Paula V
authors.initials: AP
authors.lastname: Dantas
authors.forename: Robin
authors.initials: R
authors.lastname: Looft-Wilson
authors.forename: Takahisa
authors.initials: T
authors.lastname: Murata
authors.forename: Salvatore
authors.initials: S
authors.lastname: Salomone
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.forename: Cenk
authors.initials: C
authors.lastname: Ayata
authors.forename: Michael A
authors.initials: MA
authors.lastname: Moskowitz
authors.forename: Thomas
authors.initials: T
authors.lastname: Michel
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
authors.forename: Paul L
authors.initials: PL
authors.lastname: Huang
mesh_terms: D000409:Alanine / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000235:genetics / Q000378:metabolism; D002545:Brain Ischemia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D002536:Cerebral Arteries / Q000201:enzymology / Q000293:injuries; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation; D012039:Regional Blood Flow; D012694:Serine / Q000235:genetics / Q000378:metabolism; D020521:Stroke / Q000201:enzymology / Q000235:genetics / Q000473:pathology
chemical_list: D001224:Aspartic Acid; D012694:Serine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000409:Alanine