The phosphorylation state of eNOS modulates vascular reactivity and outcome of cerebral ischemia in vivo.
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.
Atochin
Dmitriy N
DN
Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, MA 02129, USA.
Wang
Annie
A
Liu
Victor W T
VW
Critchlow
Jeffrey D
JD
Dantas
Ana Paula V
AP
Looft-Wilson
Robin
R
Murata
Takahisa
T
Salomone
Salvatore
S
Shin
Hwa Kyoung
HK
Ayata
Cenk
C
Moskowitz
Michael A
MA
Michel
Thomas
T
Sessa
William C
WC
Huang
Paul L
PL
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
D001224:Aspartic Acid; D012694:Serine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000409:Alanine