Abstract W MP77: The Role of Ischemia/Reperfusion Generated Nitrative Stress on VEGF Angiogenic Signaling in Diabetic rats.

Diabetes worsens the outcome and impairs recovery after stroke. We have previously shown that diabetes caused a nitration-dependent dysfunctional cerebral neovascularization via increased vascular endothelial growth factor (VEGF) signalling. Our recent study showed that ischemia/reperfusion (I/R) impaired vascular repair in the post-stroke period in diabetes. Yet, the molecular mechanism is unclear. Our present hypothesis is that I/R-mediated excess peroxynitrite formation impairs VEGF survival and angiogenic signal in a nitration-dependent manner. Methods: Acute ischemic stroke was induced via 90 min middle cerebral artery occlusion in Wistar (Wis) and diabetic Goto-Kakizaki rats (GK). 14 days later brain sections were examined for peroxynitrite generation (nitrotyrosine), survival markers (Akt and P38 activation), and apoptosis markers (caspase-3 and cleaved PARP). Brain micro-vascular endothelial cells (BMVEC) were isolated from Wis and GK rats and subjected to 6 hr hypoxia (0.2% oxygen) followed by 18...