title: Arsenite suppresses angiogenesis of vascular endothelial cells mediated by Platelet Derived Growth Factor Receptor-beta.
abstract: The present study aimed to investigate the effects of sodium arsenite (NaAsO2) on the angiogenesis of human umbilical vein endothelial cells (HUVECs) and the mechanism involved. Firstly, a Matrigel-based in vitro angiogenesis assay demonstrated that arsenite suppressed the angiogenesis of HUVECs in a dose-dependent manner. Then by using a global inhibitor for multiple growth factor receptors (E7080) and a specific inhibitor of PDGFR-beta (CP-673451), we found that E7080 completely prevented and CP-673451 significantly decreased the angiogenesis of HUVECs. This suggested that angiogenesis of HUVECs depends on the signal pathway mediated by tyrosine kinase receptors and that among them, PDGFR-beta has an important regulatory function. Finally by using porcine aortic endothelial cells which stably express human PDGFR-beta, we found that arsenite suppressed the angiogenesis mediated by PDGFR-beta. Based on these results, we conclude that arsenite suppressed the angiogenesis of the vascular endothelial cells, that this effect is mediated by PDGFR-beta, and postulate that it might contribute to the injuries of blood vessel in arsenism.
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, China; The Second Hospital of Jilin University, Changchun, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Mou
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yue
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Xuejin
authors.initials: X
authors.lastname: Su
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, China. Electronic address: lirg@jlu.edu.cn.
authors.forename: Ronggui
authors.initials: R
authors.lastname: Li
authors.affiliation: Life Science Research Center, Beihua University, Jilin, PR China. Electronic address: sunxinbh@126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001562:Benzimidazoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010671:Phenylurea Compounds / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D017670:Sodium Compounds / Q000633:toxicity*; D013552:Swine; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D020533:Angiogenesis Inhibitors; D018053:Arsenites; D001562:Benzimidazoles; C497448:CP-673,451; D010671:Phenylurea Compounds; D011804:Quinolines; D017670:Sodium Compounds; D014874:Water Pollutants, Chemical; C017947:sodium arsenite; D020797:Receptor, Platelet-Derived Growth Factor beta; C531958:lenvatinib
keywords: Angiogenesis; Arsenic; Human umbilical vein endothelial cells; Platelet derived growth factor receptor