title: Glipizide suppresses embryonic vasculogenesis and angiogenesis through targeting natriuretic peptide receptor A.
abstract: 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.
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou 510006, China; School of Basic Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Quliang
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology & Embryology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Chaojie
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology & Embryology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Han
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology & Embryology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology & Embryology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Jiangchao
authors.initials: J
authors.lastname: Li
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Qi
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology & Embryology, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: yang_xuesong@126.com.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: wanglijing62@163.com.
authors.forename: Lijing
authors.initials: L
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D058750:Epithelial-Mesenchymal Transition; D054262:Gastrulation; D015870:Gene Expression; D005913:Glipizide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D015017:Yolk Sac / Q000098:blood supply
chemical_list: D020533:Angiogenesis Inhibitors; D007004:Hypoglycemic Agents; D040301:Vascular Endothelial Growth Factor Receptor-2; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D005913:Glipizide
keywords: Chick embryo; Glipizide; Natriuretic peptide receptor; Vasculogenesis