Angiostatin及其内部Kringle结构域抗新生血管分子机制的研究进展

Molecular mechanism of Angiostatin and its internal Kringle domains for angiogenesis

新生血管性眼病是一类难以逆转、治疗棘手的致盲性眼疾，其发病率呈逐年增长趋势，包括年龄相关性黄斑变性、增生性糖尿病视网膜病变、角膜新生血管及新生血管性青光眼等。治疗此类疾病的关键在于抑制新生血管生长。Angiostatin是一种内生性的新生血管抑制剂，由水解纤溶酶原形成，包含纤溶酶原5个Kringle结构域的一种或多种的不同片段。Angiostatin定向作用于血管内皮细胞，抑制内皮细胞的增殖、迁移、侵袭及管腔形成，并诱导其凋亡，从而起到抗新生血管的作用。鉴于目前此类研究已引起同行关注，因此，有必要就Angiostatin抗新生血管的分子机制研究进展予以综述，以期为Angiostatin的临床应用及新生血管性眼病的治疗研究开辟新思路。

Ocular neovascularization is a sight-threatening condition involved in several pathologic ocular disorders such as corneal neovaseularization, retinopathy of prematurity, proliferative diabetic retinopathy ,age-related macular degeneration, and neovaseular glaucoma. Angiostatin, a naturally occurring inhibitor of angiogenesis,was discovered based on its ability to block tumor growth in vivo by inhibiting the formation of new tumor blood vessels. Angiostatin is a proteolytically derived internal fragment of plasminogen and may contain various members of the five plasminogen ＇ Kringle ＇ domains. Angiostatin＇ s molecular mechanism of anti-angiogenesis includes inhibiting endothelial cell proliferation, migration and tubule formation,and also inducing endothelial cells apoptosis. A number of groups have sought to identify the cell surface binding sites for Angiostatin, resulting in many different binding sites proposed for Angiostatin on the surface of endothelial cells. This review will consider the research supporting all of the various reported Angiostatin binding sites. There have been several developments in the quest to elucidate the mechanism of action of Angiostatin and the regulation of its receptor. The purpose of this review is to describe the highlights of research on the mechanism of action of Angiostatin, and then assess the therapeutic value of this peptide.