权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Role of endothelial cells and pericyte interdigitation in angiogenesis

内皮细胞和周细胞交错在血管生成中的作用

基本信息

批准号：
15580267
负责人：
WAKUI Shin
金额：
$ 2.43万
依托单位：
Azabu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

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.

内皮细胞和周细胞在血管生成中起关键作用，其部分由血管生成素（Ang）/Tie-2系统和血管内皮生长因子（VEGF）控制。内皮细胞和周细胞相互指配（EPI），包括周细胞的胞质突起和相应的内皮凹陷，经常出现在血管生成部位。在大鼠皮下植入热可逆凝胶化聚合物圆盘后，毛细血管密度在第5天较低，在第7天增加到峰值，然后在第10-20天降低。在第5天观察到少量EPI，然后在第10天急剧增加至峰值，但在第20天下降。光镜和电镜免疫组化及RNA原位杂交分析显示，Tie-2定位于内皮细胞，Ang-2定位于内皮细胞和周细胞，Ang-1和VEGF定位于周细胞，且Ang-1在周细胞EPI处表达最强。常规、定量RT-PCR和Western blot分析显示，Ang-1水平在第5-7天较低，然后在第10-20天升高，而VEGF水平在第5-10天较高，但在第20天下降。Ang-2和Tie-2的表达在第5-20天没有变化。本研究表明，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可能作为一种途径，为Ang-1/Tie-2系统与VEGF促进周细胞募集微血管的完整性。