title: Deficiency of the microRNA-31-microRNA-720 pathway in the plasma and endothelial progenitor cells from patients with coronary artery disease.
abstract: OBJECTIVE
  Defects in angiogenesis/vasculogenesis or vessel repair are major complications of coronary artery disease (CAD). Endothelial progenitor cells (EPCs) play a fundamental role in postnatal vascular repair and CAD. The role of microRNAs in CAD pathogenesis and their potential as biomarkers remain to be elucidated.
  
  
  RESULTS
  MicroRNA-31 (miR-31) level in both the plasma and EPCs of patients with CAD is found lower. miR-31 regulates EPC activities by targeting FAT atypical cadherin 4 and thromboxane A2 receptor, which show increased expression in CAD EPCs. Overexpressing miR-31 in CAD EPCs rescued their angiogenic and vasculogenic abilities both in vitro and in vivo. When exploring approaches to restore endogenous miR-31, we found that far-infrared treatment enhanced the expression of not only miR-31, but also miR-720 in CAD EPCs. miR-720, which was also decreased in EPCs and the plasma of patients with CAD, stimulated EPC activity by targeting vasohibin 1. The miR720-vasohibin 1 pair was shown to be downstream of FAT atypical cadherin 4, but not of thromboxane A2 receptor. FAT atypical cadherin 4 inhibited miR-720 expression via repression of the planar cell polarity signaling gene four-jointed box 1 (FJX1), which was required for miR-720 expression through a hypoxia-inducible factor 1, α subunit-dependent mechanism. Restoring miR-720 level strengthened activity of CAD EPCs. The miR-31-miR-720 pathway is shown critical to EPC activation and that downregulation of this pathway contributes to CAD pathogenesis. Circulating levels of miR-31, miR-720, and vasohibin 1 have the potential to allow early diagnosis of CAD and to act as prognosis biomarkers for CAD and other EPC-related diseases.
  
  
  CONCLUSIONS
  Manipulating the expression of the miR-31-miR-720 pathway in malfunction EPCs should help develop novel therapeutic modalities.
authors.affiliation: From the Institute of Microbiology and Immunology, School of Life Science (H.-W.W., T.-S.H., H.-H.L., K.-H.L., C.-F.T., Y.-C.C., Y.-L.C.), Cancer Research Center & Genome Research Center (H.-W.W.), School of Medicine (P.-H.H., C.-C.L.), and Cardiovascular Research Center (P.-H.H.), National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine (P.-H.H.) and Division of Nephrology, Department of Medicine (C.-C.L.), Taipei Veterans General Hospital, Taipei, Taiwan ; Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (H.-W.W.); Department of Obstetrics and Gynecology, Hsin-Chu Mackay Memorial Hospital, Hsin Chu, Taiwan (S.-J.C., C.-H.T., C.-H.C.); and Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (T.-N.T., C.-C.C., S.-M.C.).
authors.forename: Hsei-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Tse-Shun
authors.initials: TS
authors.lastname: Huang
authors.forename: Hung-Hao
authors.initials: HH
authors.lastname: Lo
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Lin
authors.forename: Shing-Jyh
authors.initials: SJ
authors.lastname: Chang
authors.forename: Ko-Hsun
authors.initials: KH
authors.lastname: Liao
authors.forename: Chin-Han
authors.initials: CH
authors.lastname: Tsai
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Chan
authors.forename: Cheng-Fong
authors.initials: CF
authors.lastname: Tsai
authors.forename: Yi-Chieh
authors.initials: YC
authors.lastname: Cheng
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Chiu
authors.forename: Tsung-Neng
authors.initials: TN
authors.lastname: Tsai
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Cheng
authors.forename: Shu-Meng
authors.initials: SM
authors.lastname: Cheng
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism* / Q000528:radiation effects / Q000637:transplantation; D005819:Genetic Markers; D006614:Hindlimb; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007259:Infrared Rays; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000097:blood*; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D009841:Oligonucleotides / Q000378:metabolism; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000378:metabolism; D020127:Recovery of Function; D012039:Regional Blood Flow; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism* / Q000528:radiation effects; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D015820:Cadherins; D018797:Cell Cycle Proteins; C534294:FAT4 protein, human; D005819:Genetic Markers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C534612:MIRN31 microRNA, human; C568636:MIRN720 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D025521:Tumor Suppressor Proteins; C493181:VASH1 protein, human
keywords: coronary artery disease; microRNAs