title: Intermedin restricts vessel sprouting by inhibiting the loosening of endothelial junction.
abstract: Vessel sprouting from pre-existing vasculature is a key step for the formation of a functional vasculature. The low level of vascular endothelial growth factor (VEGF) induces normal and stable angiogenesis, whereas high level of VEGF causes irregular and over sprouted vasculature. Intermedin (IMD) is a novel member of calcitonin family, and was found to be able to restrict the excessive vessel sprouting. However, the underlying mechanism had not been elucidated. In this study, using in vitro and in vivo angiogenic models, we found that the loosening of endothelial junction could significantly increase the ability of low-dose VEGF to induce vessel sprouting. IMD inhibited the junction dissociation-induced vessel sprouting by re-establishing the complex of vascular endothelial cadherin on the cell-cell contact. Our findings suggested a novel mechanism through which IMD could restrict the excessive vessel sprouting by preventing the endothelial junction from dissociation, and provide new insight into the understanding of the regulation of sprouting angiogenesis.
authors: Department of Intensive Care Unit of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors: Fei
authors: F
authors: Xiao
authors: Molecular Medicine Research Center, West China Hospital, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors: Li-jun
authors: LJ
authors: Wang
authors: Molecular Medicine Research Center, West China Hospital, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors: Huan
authors: H
authors: Zhao
authors: Molecular Medicine Research Center, West China Hospital, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors: Chun
authors: C
authors: Tan
authors: Molecular Medicine Research Center, West China Hospital, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors: De-nian
authors: DN
authors: Wang
authors: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors: Heng
authors: H
authors: Zhang
authors: Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors: Yong-gang
authors: YG
authors: Wei
authors: Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, PR China. Electronic address: scujinliu@gmail.com.
authors: Jin
authors: J
authors: Liu
authors: Molecular Medicine Research Center, West China Hospital, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, Sichuan, PR China. Electronic address: zhangweifv@163.com.
authors: Wei
authors: W
authors: Zhang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D007365:Intercellular Junctions / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000378:metabolism; D036361:Peptide Hormones / Q000378:metabolism* / Q000494:pharmacology; D012160:Retina / Q000166:cytology / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D009479:Neuropeptides; D036361:Peptide Hormones; D042461:Vascular Endothelial Growth Factor A; D000099152:Cadherin 5; C484330:ADM2 protein, human; C514552:intermedin protein, mouse
keywords: Angiogenesis; Intermedin; Sprouting; VE-cadherin; VEGF