Transgenic mice expressing a phosphomimetic (S1179D) form of eNOS developed less severe strokes and had improved cerebral blood flow compared to mice expressing an unphosphorylatable (S1179A) form.
Does the phosphorylation state of eNOS modulate vascular reactivity and stroke size in a mouse model of cerebral ischemia?
The phosphorylation state of eNOS at serine 1179 is a critical determinant of vascular reactivity and stroke severity in vivo, providing a molecular mechanism linking cardiovascular risk factors to vascular disease.
Absolute Event Rate: 1.57% vs 2.67%
p-value: p=<0.05
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 et al. (Thu,) conducted a other in Cerebral ischemia. S1179D eNOS transgene (phosphomimetic) vs. S1179A eNOS transgene (unphosphorylatable) was evaluated on Neurologic score at 23 hours post-ischemia (p=<0.05). Transgenic mice expressing a phosphomimetic (S1179D) form of eNOS developed less severe strokes and had improved cerebral blood flow compared to mice expressing an unphosphorylatable (S1179A) form.