title: Arsenic-induced anti-angiogenesis via miR-425-5p-regulated CCM3.
abstract: Human exposure to drinking water contaminated with arsenic is a serious global health concern and it predisposes people to cardiovascular diseases, such as hypertension, atherosclerosis, and microvascular diseases. Although accumulating evidence supports a role for angiogenesis responses to arsenic in the pathogenesis of the cardiovascular disease, the detailed molecular mechanism is not well understood. We aimed to determine the role and mechanism of microRNA (miRNA) in arsenic-induced angiogenesis. In our present study, sodium arsenite (NaAsO2) inhibited angiogenesis by decreasing cells proliferation, migration and tube formation in HUVECs. After NaAsO2 treatment, we found the expression of microRNA-425-5p (miR-425-5p) was reduced in vitro and in vivo and over-expression of miR-425-5p reversed the NaAsO2-induced anti-angiogenesis through its direct target cerebral cavernous malformation 3 (CCM3). Furthermore, we showed that NaAsO2 up-regulated CCM3 expression in vitro and in vivo. In addition, we demonstrated that inhibition of Notch and activation of VEGF/p38 signaling were involved in miR-425-5p blocking NaAsO2-induced anti-angiogenesis.
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Risk Assessment, Sun Yat-sen University, School of Public Health, Guangzhou, Guangdong 510080, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Yuzhu
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Risk Assessment, Sun Yat-sen University, School of Public Health, Guangzhou, Guangdong 510080, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Xing
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Risk Assessment, Sun Yat-sen University, School of Public Health, Guangzhou, Guangdong 510080, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Risk Assessment, Sun Yat-sen University, School of Public Health, Guangzhou, Guangdong 510080, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Risk Assessment, Sun Yat-sen University, School of Public Health, Guangzhou, Guangdong 510080, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: The Center for Translational Medicine, The first Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China; Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: The Center for Translational Medicine, The first Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China. Electronic address: wdji2008@163.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Ji
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Risk Assessment, Sun Yat-sen University, School of Public Health, Guangzhou, Guangdong 510080, China. Electronic address: heyun_jane@163.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: He
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D018053:Arsenites / Q000633:toxicity*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017670:Sodium Compounds / Q000633:toxicity*; D014162:Transfection; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D051017:Apoptosis Regulatory Proteins; D018053:Arsenites; C555677:MIRN425 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins; D051880:Receptors, Notch; D017670:Sodium Compounds; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C017947:sodium arsenite; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Angiogenesis; Arsenic; MicroRNA-425-5p; Signaling pathway