Activated microvessels express vascular endothelial growth factor and integrin alpha(V)beta(3) during focal cerebral ischemia

Both vascular endothelial growth factor (VEGF) and integrin alpha(v)beta(3) play roles in angiogenesis. In noncerebral vascular systems, VEGF can indu ce endothelial integrin alpha(v)beta(3) expression. However, it is unknown whether VEGF, like integrin alpha(v)beta(3) appears in the initial response of microvessels to focal brain ischemia. Their coordinate expression in mi crovessels of the basal ganglia after middle cerebral artery occlusion (MCA O) in the nonhuman primate model was examined quantitatively. Cells incorpo rating deoxyuridine triphosphate (dUTP(+)) by the polymerase I reaction at 1 hour (n = 3), 2 hours (n = 3), and 7 days (n = 4) after MCAO defined the ischemic core (Ic) and peripheral regions. Both VEGF and integrin alpha(v)b eta(3) were expressed by activated noncapillary (7.5- to 30.0-mu m diameter ) microvessels in the Ic region at 1 and 2 hours after MCAO. At 7 days afte r MCAO, the number of VEGF(+), integrin alpha(v)beta(3)(+), or proliferatin g cell nuclear antigen-positive microvessels had decreased within the Ic re gion. The expressions of VEGF, integrin alpha(v)beta(3) and proliferating c ell nuclear antigen were highly correlated on the same microvessels using h ierarchical log-linear statistical models. Also, VEGF and subunit alpha(v) messenger ribonucleic acids were coexpressed on selected microvessels. Here , noncapillary microvessels are activated specifically early during a focal cerebral ischemic insult and rapidly express VEGF and integrin alpha(v)bet a(3) together.