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整合素αvβ3拮抗剂可阻止胚胎期新生血管形成过程中的血管成熟。

An antagonist of integrin alpha v beta 3 prevents maturation of blood vessels during embryonic neovascularization.

作者信息

Drake C J, Cheresh D A, Little C D

机构信息

Department of Cell Biology, Medical University of South Carolina, Charleston 29425, USA.

出版信息

J Cell Sci. 1995 Jul;108 ( Pt 7):2655-61. doi: 10.1242/jcs.108.7.2655.

DOI:10.1242/jcs.108.7.2655
PMID:7593306
Abstract

Experimental data in this study demonstrate that integrin alpha v beta 3 is fundamentally involved in the maturation of blood vessels during embryonic neovascularization (vasculogenesis). Integrin alpha v beta 3 was specifically expressed on the surface of angioblasts during vessel development in quail embryos and vitronectin, a ligand for alpha v beta 3, localized to the basal surface of these cells. More importantly, microinjection of the anti-alpha v beta 3 monoclonal antibody, LM609, disrupted the normal pattern of vascular development. After exposure to LM609 the angioblasts in experimental embryos appeared as clusters of rounded cells lacking normal cellular protrusions. This led to disruption of lumen formation and abnormal vessel patterning. These findings demonstrate that during vasculogenesis ligation of integrin alpha v beta 3 on the surface of primordial endothelial cells is critical for the differentiation and maturation of blood vessels. Similar studies on chicken chorioallantoic membrane showed that LM609 blocks angiogenesis. Together the two studies suggest that integrin alpha v beta 3 plays a role in neovascularization of tissues.

摘要

本研究中的实验数据表明,整合素αvβ3在胚胎新生血管形成(血管发生)过程中对血管成熟起着根本性作用。在鹌鹑胚胎血管发育过程中,整合素αvβ3特异性表达于成血管细胞表面,而αvβ3的配体玻连蛋白则定位于这些细胞的基底表面。更重要的是,显微注射抗αvβ3单克隆抗体LM609会破坏血管发育的正常模式。暴露于LM609后,实验胚胎中的成血管细胞呈现为缺乏正常细胞突起的圆形细胞簇。这导致管腔形成受阻和血管模式异常。这些发现表明,在血管发生过程中,原始内皮细胞表面整合素αvβ3的结合对于血管的分化和成熟至关重要。对鸡胚绒毛尿囊膜的类似研究表明,LM609可阻断血管生成。这两项研究共同表明,整合素αvβ3在组织新生血管形成中发挥作用。

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