Beck H, Acker T, Wiessner C, Allegrini P R, Plate K H
Abteilung Neuropathologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Am J Pathol. 2000 Nov;157(5):1473-83. doi: 10.1016/S0002-9440(10)64786-4.
Vascular endothelial growth factor (VEGF), a key regulator of vasculogenesis and embryonic angiogenesis, was recently found to be up-regulated in an animal model of stroke. Unlike VEGF, angiopoietin (Ang)-1 and -2, their receptor tie-2, and the associated receptor tie-1 exert their functions at later stages of vascular development, i.e., during vascular remodeling and maturation. To assess the role of the angiopoietin/tie family in ischemia-triggered angiogenesis we analyzed their temporal and spatial expression pattern after middle cerebral artery occlusion (MCAO) using in situ hybridization and immunohistochemistry. Ang-1 mRNA was constitutively expressed in a subset of glial and neuronal cells with no apparent change in expression after MCAO. Ang-2 mRNA was up-regulated 6 hours after MCAO and was mainly observed in endothelial cell (EC) cord tips in the peri-infarct and infarct area. Up-regulation of both Ang-2 and VEGF coincided with EC proliferation. Interestingly, EC proliferation was preceded by a transient period of EC apoptosis, correlating with a change in VEGF/Ang-2 balance. Our observation of specific stages of vascular regression and growth after MCAO are in agreement with recent findings suggesting a dual role of Ang-2 in blood vessel formation, depending on the availability of VEGF.
血管内皮生长因子（VEGF）是血管生成和胚胎血管生成的关键调节因子，最近发现在中风动物模型中其表达上调。与VEGF不同，血管生成素（Ang）-1和-2、它们的受体Tie-2以及相关受体Tie-1在血管发育的后期发挥作用，即在血管重塑和成熟过程中。为了评估血管生成素/Tie家族在缺血触发的血管生成中的作用，我们使用原位杂交和免疫组织化学分析了大脑中动脉闭塞（MCAO）后它们的时空表达模式。Ang-1 mRNA在一部分神经胶质细胞和神经元细胞中组成性表达，MCAO后表达无明显变化。Ang-2 mRNA在MCAO后6小时上调，主要在梗死周边和梗死区域的内皮细胞（EC）索末端观察到。Ang-2和VEGF的上调与EC增殖同时发生。有趣的是，EC增殖之前有一个短暂的EC凋亡期，这与VEGF/Ang-2平衡的变化相关。我们对MCAO后血管消退和生长特定阶段的观察与最近的研究结果一致，这些结果表明Ang-2在血管形成中具有双重作用，这取决于VEGF的可用性。
