Role of endothelial cells and pericyte interdigitation in angiogenesis

血管内皮细胞和周细胞在血管生成中起关键作用，血管生成素(Ang)/Tie-2系统和血管内皮生长因子(VEGF)在一定程度上控制着血管生成。内皮细胞和周细胞交错(EPI)由周细胞的胞质突起和相应的内皮凹陷组成，常见于血管生成部位。大鼠皮下植入热可逆凝胶聚合物盘后，第5天毛细血管密度较低，第7天达到高峰，第10~20天开始下降。免疫组织化学和RNA原位杂交显示Tie-2定位于内皮细胞，Ang-2定位于内皮细胞和周细胞，Ang-1定位于周细胞，Ang-1定位于周细胞。常规、定量RT-PCR和Western印迹分析显示，Ang-1在5~7天低表达，10~20天升高，而血管内皮生长因子在5~10天高表达，20天有所下降，5~20天Ang-2和Tie-2表达无明显变化。目前的研究表明，血管生成期可能由Ang-2和VEGF启动，而微血管成熟期可能由Ang-1和VEGF启动。此外，EPI可能作为Ang-1/Tie-2系统的一条通路，而血管内皮生长因子促进周细胞募集微血管的完整性。

Endothelial cells and pericytes play critical role in angiogenesis, which is controlled, in part, by the angiopoietin (Ang)/Tie-2 system and vascular endothelial growth factor (VEGF). Endothelial cell and pericyte interdigitations(EPI), consisting of cytoplasmic projections of pericytes and corresponding endothelial indentations, are frequently present at angiogenic sites. After subcutaneous implantation of a thermoreversible gelation polymer disc in rats, the capillary density was low on day 5, increased to a peak on day 7, and then decreased on days 10-20. A small number of EPI were observed on day 5, then increased sharply to a peak on day 10, but had decreased on day 20. Light and electron microscopy immunohistochemical and RNA in situ hybridization analyses revealed that Tie-2 localized at endothelial cells, and Ang-2 localized at endothelial cells and pericytes, while Ang-1 and VEGF localized at pericytes, and Ang-1 was most intensely observed at EPI of pericytes. Conventional, quantitative RT-PCR and Western blot analyses revealed that the level of Ang-1 was low on days 5-7, and then increased on days 10-20, while the level of VEGF was high on days 5-10, but had decreased on day 20. The expression of Ang-2 and Tie-2 was unchanged on days 5-20. The present study showed that the angiogenic phase might be initiated by Ang-2 and VEGF, while the microvessel maturation phase might to be initiated by Ang-1 and VEGF. Moreover, EPI might act as a pathway for the Ang-1/Tie-2 system with VEGF promoting pericyte recruitment for microvascular integrity.