title: Dysregulation of Vascular Endothelial Growth Factor Receptor-2 by Multiple miRNAs in Endothelial Colony-Forming Cells of Coronary Artery Disease.
abstract: Endothelial colony-forming cells (ECFCs) have the potential to be used in regenerative medicine. Dysfunction of ECFCs is correlated with the onset of cardiovascular disorders, especially coronary artery disease (CAD). Binding of vascular endothelial growth factor A (VEGFA) to vascular endothelial growth factor receptor-2 (VEGFR2) triggers cell motility and angiogenesis of ECFCs, which are crucial to vascular repair.
  
  
  
  To identify the miRNA-VEGFR2-dependent regulation of ECFC functions, ECFCs isolated from peripheral blood of disease-free and CAD individuals were subjected to small RNA sequencing for identification of anti-VEGFR2 miRNAs. The angiogenic activities of the miRNAs were determined in both in vitro and in vivo mice models.
  
  
  
  Three miRNAs, namely miR-410-3p, miR-497-5p, and miR-2355-5p, were identified to be upregulated in CAD-ECFCs, and VEGFR2 was their common target gene. Knockdown of these miRNAs not only restored the expression of VEGFR2 and increased angiogenic activities of CAD-ECFCs in vitro, but also promoted blood flow recovery in ischemic limbs in vivo. miR-410-3p, miR-497-5p, and miR-2355-5p could serve as potential biomarkers for CAD detection as they are highly expressed in the plasma of CAD patients.
  
  
  
  This modulation could help develop new therapeutic modalities for cardiovascular diseases and other vascular dysregulated diseases, especially tumor angiogenesis.
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Shu-Han
authors.initials: SH
authors.lastname: Su
authors.forename: Chun-Hsien
authors.initials: CH
authors.lastname: Wu
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Chiu
authors.forename: Shing-Jyh
authors.initials: SJ
authors.lastname: Chang
authors.forename: Hung-Hao
authors.initials: HH
authors.lastname: Lo
authors.forename: Ko-Hsun
authors.initials: KH
authors.lastname: Liao
authors.forename: Cheng-Fong
authors.initials: CF
authors.lastname: Tsai
authors.forename: Tsung-Neng
authors.initials: TN
authors.lastname: Tsai
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Shu-Meng
authors.initials: SM
authors.lastname: Cheng
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Cheng
authors.forename: Hsei-Wei
authors.initials: HW
authors.lastname: Wang
mesh_terms: D000818:Animals; D000070416:Antagomirs / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D019295:Computational Biology; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006614:Hindlimb; D006801:Humans; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic; D020127:Recovery of Function; D012039:Regional Blood Flow; D013997:Time Factors; D014162:Transfection; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000070416:Antagomirs; C568527:MIRN410 microRNA, human; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; C000588866:KDR protein, human; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2