Activated Microvessels Express Vascular Endothelial Growth Factor and Integrin αvβ3 During Focal Cerebral Ischemia

Abstract

Both vascular endothelial growth factor (VEGF) and integrin α_vβ₃ play roles in angiogenesis. In noncerebral vascular systems, VEGF can induce endothelial integrin α_vβ₃ expression. However, it is unknown whether VEGF, like integrin α_vβ₃, appears in the initial response of microvessels to focal brain ischemia. Their coordinate expression in microvessels of the basal ganglia after middle cerebral artery occlusion (MCAO) in the nonhuman primate model was examined quantitatively. Cells incorporating 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 α_vβ₃ were expressed by activated noncapillary (7.5- to 30.0-μm diameter) microvessels in the Ic region at 1 and 2 hours after MCAO. At 7 days after MCAO, the number of VEGF+, integrin α_vβ₃⁺, or proliferating cell nuclear antigen-positive microvessels had decreased within the Ic region. The expressions of VEGF, integrin α_vβ₃, and proliferating cell nuclear antigen were highly correlated on the same microvessels using hierarchical log-linear statistical models. Also, VEGF and subunit α_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 α_vβ₃ together.