Liu Wei, Hajjar Katherine A
Biol Chem. 2016 Oct 1;397(10):1005-16. doi: 10.1515/hsz-2016-0166.
The formation of new blood vessels from pre-existing vasculature, the process known as angiogenesis, is highly regulated by pro- and anti-angiogenic signaling molecules including growth factors and proteases. As an endothelial cell-surface co-receptor for plasminogen and tissue plasminogen activator, the annexin A2 (ANXA2) complex accelerates plasmin generation and facilitates fibrinolysis. Plasmin can subsequently activate a downstream proteolytic cascade involving multiple matrix metalloproteinases. Thus, in addition to maintaining blood vessel patency, the ANXA2 complex can also promote angiogenesis via its pro-fibrinolytic activity. The generation of ANXA2-deficient mice allowed us to first observe the pro-angiogenic role of ANXA2 in vivo. Further investigations have provided additional details regarding the mechanism for ANXA2 regulation of retinal and corneal angiogenesis. Other studies have reported that ANXA2 supports angiogenesis in specific tumor-related settings. Here, we summarize results from in vivo studies that illustrate the pro-angiogenic role of ANXA2, and discuss the critical questions that may lead to an advanced understanding of the molecular mechanisms for ANXA2-mediated angiogenesis. Finally, highlights from studies on ANXA2-interacting agents offer potential therapeutic opportunities for the application of ANXA2-centered pharmaceuticals in angiogenesis-related disorders.
从已有的脉管系统形成新血管，即血管生成过程，受到包括生长因子和蛋白酶在内的促血管生成和抗血管生成信号分子的高度调控。作为纤溶酶原和组织纤溶酶原激活物的内皮细胞表面共受体，膜联蛋白A2（ANXA2）复合物加速纤溶酶生成并促进纤维蛋白溶解。纤溶酶随后可激活涉及多种基质金属蛋白酶的下游蛋白水解级联反应。因此，除了维持血管通畅外，ANXA2复合物还可通过其促纤维蛋白溶解活性促进血管生成。ANXA2基因敲除小鼠的产生使我们首次在体内观察到ANXA2的促血管生成作用。进一步的研究提供了关于ANXA2调节视网膜和角膜血管生成机制的更多细节。其他研究报道ANXA2在特定肿瘤相关环境中支持血管生成。在这里，我们总结了体内研究结果，这些结果说明了ANXA2的促血管生成作用，并讨论了可能有助于深入理解ANXA2介导的血管生成分子机制的关键问题。最后，关于ANXA2相互作用剂的研究亮点为以ANXA2为中心的药物在血管生成相关疾病中的应用提供了潜在的治疗机会。
