Activated microvessels express vascular endothelial growth factor and integrin αVβ3 during focal cerebral ischemia

Activated microvessels express vascular endothelial growth factor and integrin αVβ3 during focal cerebral ischemia
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DOI:
10.1097/00004647-199909000-00012
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发表时间:
1999-09-01
影响因子:
6.3
通讯作者:
del Zoppo, GJ
del Zoppo, GJ
中科院分区:
医学1区
文献类型:
--
作者:
Abumiya, T;Lucero, J;del Zoppo, GJ

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血管内皮生长因子(VEGF)和整合素α(V)β(3)在血管生成中起作用。在非脑血管系统中,VEGF可诱导内皮整合素α(v)β(3)表达。然而,目前尚不清楚VEGF是否像整合素α(v)β(3)一样出现在微血管对局灶性脑缺血的初始反应中。在非人灵长类动物大脑中动脉闭塞(MCAO)模型中,定量检测了它们在基底节微血管中的协调表达。在MCAO后1小时(n = 3)、2小时(n = 3)和7天(n = 4)通过聚合酶I反应掺入脱氧尿苷三磷酸(dUTP(+))的细胞确定缺血核心(Ic)和外周区域。在MCAO后1和2小时,血管内皮生长因子和整合素α(v)β(3)在Ic区的激活的非毛细血管(直径7.5- 30.0 μ m)微血管中表达。在MCAO后7天,血管内皮生长因子(+)、整合素α(v)β(3)(+)或增殖细胞核抗原阳性微血管的数量在Ic区域内减少。使用分层对数线性统计模型,VEGF、整合素α(v)β(3)和增殖细胞核抗原的表达在相同的微血管上高度相关。此外,VEGF和亚基α(v)信使核糖核酸在选定的微血管上共表达。在此,非毛细血管微血管在局灶性脑缺血损伤的早期被激活,并快速表达VEGF和整合素α(v)β(3)。
Both vascular endothelial growth factor (VEGF) and integrin alpha(v)beta(3) play roles in angiogenesis. In noncerebral vascular systems, VEGF can induce 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 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)beta(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 after MCAO, the number of VEGF(+), integrin alpha(v)beta(3)(+), or proliferating cell nuclear antigen-positive microvessels had decreased within the Ic region. The expressions of VEGF, integrin alpha(v)beta(3) 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)beta(3) together.