Abumiya T, Lucero J, Heo J H, Tagaya M, Koziol J A, Copeland B R, del Zoppo G J
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
J Cereb Blood Flow Metab. 1999 Sep;19(9):1038-50. doi: 10.1097/00004647-199909000-00012.
Both vascular endothelial growth factor (VEGF) and integrin alpha(v)beta3 play roles in angiogenesis. In noncerebral vascular systems, VEGF can induce endothelial integrin alpha(v)beta3 expression. However, it is unknown whether VEGF, like integrin alpha(v)beta3, 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 alpha(v)beta3 were expressed by activated noncapillary (7.5- to 30.0-microm diameter) microvessels in the Ic region at 1 and 2 hours after MCAO. At 7 days after MCAO, the number of VEGF+, integrin alpha(v)beta3+, or proliferating cell nuclear antigen-positive microvessels had decreased within the Ic region. The expressions of VEGF, integrin alpha(v)beta3, and proliferating cell nuclear antigen were highly correlated on the same microvessels using hierarchical 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)beta3 together.
血管内皮生长因子（VEGF）和整合素α(v)β3均在血管生成过程中发挥作用。在非脑血管系统中，VEGF可诱导内皮整合素α(v)β3的表达。然而，VEGF是否像整合素α(v)β3一样，出现在微血管对局灶性脑缺血的初始反应中尚不清楚。我们定量检测了非人类灵长类动物模型大脑中动脉闭塞（MCAO）后基底节微血管中它们的协同表达情况。通过聚合酶I反应在MCAO后1小时（n = 3）、2小时（n = 3）和7天（n = 4）掺入脱氧尿苷三磷酸（dUTP+）的细胞定义了缺血核心（Ic）和周边区域。MCAO后1小时和2小时，Ic区域内活化的非毛细血管（直径7.5至30.0微米）微血管表达VEGF和整合素α(v)β3。MCAO后7天，Ic区域内VEGF+、整合素α(v)β3+或增殖细胞核抗原阳性微血管数量减少。使用分层对数线性统计模型，VEGF、整合素α(v)β3和增殖细胞核抗原在同一微血管上的表达高度相关。此外，VEGF和α(v)亚基信使核糖核酸在选定的微血管上共同表达。在此，非毛细血管微血管在局灶性脑缺血损伤早期被特异性激活，并迅速共同表达VEGF和整合素α(v)β3。
