Gu Quliang, Wang Chaojie, Wang Guang, Han Zhe, Li Yan, Wang Xiaoyu, Li Jiangchao, Qi Cuiling, Xu Tao, Yang Xuesong, Wang Lijing
Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou 510006, China; School of Basic Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology & Embryology, Medical College, Jinan University, Guangzhou 510632, China.
Exp Cell Res. 2015 May 1;333(2):261-272. doi: 10.1016/j.yexcr.2015.03.012. Epub 2015 Mar 28.
Glipizide, a second-generation sulfonylurea, has been widely used for the treatment of type 2 diabetes. However, it is controversial whether or not glipizide would affect angiogenesis or vasculogenesis. In the present study, we used early chick embryo model to investigate the effect of glipizide on angiogenesis and vasculogenesis, which are the two major processes for embryonic vasculature formation as well as tumor neovascularization. We found that Glipizide suppressed both angiogenesis in yolk-sac membrane (YSM) and blood island formation during developmental vasculogenesis. Glipizide did not affect either the process of epithelial to mesenchymal transition (EMT) or mesoderm cell migration. In addition, it did not interfere with separation of smooth muscle cell progenitors from hemangioblasts. Moreover, natriuretic peptide receptor A (NPRA) has been identified as the putative target for glipizide׳s inhibitory effect on vasculogenesis. When NPRA was overexpressed or activated, blood island formation was reduced. NPRA signaling may play a crucial role in the effect of glipizide on vasculogenesis during early embryonic development.
格列吡嗪是一种第二代磺酰脲类药物，已被广泛用于治疗2型糖尿病。然而，格列吡嗪是否会影响血管生成或血管发生仍存在争议。在本研究中，我们使用早期鸡胚模型来研究格列吡嗪对血管生成和血管发生的影响，这两个过程是胚胎血管系统形成以及肿瘤新生血管形成的主要过程。我们发现格列吡嗪抑制了卵黄囊膜（YSM）中的血管生成以及发育性血管发生过程中的血岛形成。格列吡嗪既不影响上皮向间充质转化（EMT）过程，也不影响中胚层细胞迁移。此外，它不干扰平滑肌细胞祖细胞与成血管细胞的分离。此外，利钠肽受体A（NPRA）已被确定为格列吡嗪对血管发生抑制作用的假定靶点。当NPRA过表达或被激活时，血岛形成减少。NPRA信号通路可能在早期胚胎发育过程中格列吡嗪对血管发生的影响中起关键作用。
