title: miRNome traits analysis on endothelial lineage cells discloses biomarker potential circulating microRNAs which affect progenitor activities.
abstract: BACKGROUND
  Endothelial progenitor cells (EPCs) play a fundamental role in not only blood vessel development but also post-natal vascular repair. Currently EPCs are defined as early and late EPCs based on their biological properties and their time of appearance during in vitro culture. Both EPC types assist angiogenesis and have been linked to ischemia-related disorders, including coronary artery disease (CAD).
  
  
  RESULTS
  We found late EPCs are more mobile than early EPCs and matured endothelial cells (ECs). To pinpoint the mechanism, microRNA profiles of early EPCs late EPCs, and ECs were deciphered by small RNA sequencing. Obtained signatures made up of both novel and known microRNAs, in which anti-angiogenic microRNAs such as miR-221 and miR-222 are more abundant in matured ECs than in late EPCs. Overexpression of miR-221 and miR-222 resulted in the reduction of genes involved in hypoxia response, metabolism, TGF-beta signalling, and cell motion. Not only hamper late EPC activities in vitro, both microRNAs (especially miR-222) also hindered in vivo vasculogenesis in a zebrafish model. Reporter assays showed that miR-222, but not miR-221, targets the angiogenic factor ETS1. In contrast, PIK3R1 is the target of miR-221, but not miR-222 in late EPCs. Clinically, both miR-221-PIK3R1 and miR-222-ETS1 pairs are deregulated in late EPCs of CAD patients.
  
  
  CONCLUSIONS
  Our results illustrate EPCs and ECs exploit unique miRNA modalities to regulate angiogenic features, and explain why late EPC levels and activities are reduced in CAD patients. These data will further help to develop new plasma biomarkers and therapeutic approaches for ischemia-related diseases or tumor angiogenesis.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Chang
authors.forename: Tse-Shun
authors.initials: TS
authors.lastname: Huang
authors.forename: Hsei-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Shing-Jyh
authors.initials: SJ
authors.lastname: Chang
authors.forename: Hung-Hao
authors.initials: HH
authors.lastname: Lo
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Chiu
authors.forename: Yen-Li
authors.initials: YL
authors.lastname: Wang
authors.forename: Chung-Der
authors.initials: CD
authors.lastname: Hsiao
authors.forename: Chin-Han
authors.initials: CH
authors.lastname: Tsai
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Chan
authors.forename: Ren-In
authors.initials: RI
authors.lastname: You
authors.forename: Chun-Hsien
authors.initials: CH
authors.lastname: Wu
authors.forename: Tsung-Neng
authors.initials: TN
authors.lastname: Tsai
authors.forename: Shu-Meng
authors.initials: SM
authors.lastname: Cheng
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. chengcc@mail.ndmctsgh.edu.tw.
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Cheng
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002478:Cells, Cultured; D058543:Class Ia Phosphatidylinositol 3-Kinase; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism*; D066026:Endothelial Progenitor Cells / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D066298:In Vitro Techniques; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D018919:Neovascularization, Physiologic; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011247:Pregnancy; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics*; D017423:Sequence Analysis, RNA; D015027:Zebrafish
chemical_list: D015415:Biomarkers; D058543:Class Ia Phosphatidylinositol 3-Kinase; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D050784:Proto-Oncogene Protein c-ets-1; C494041:ETS1 protein, human; C525709:MIR221, human; C525710:MIR222, human; C588001:PIK3R1 protein, human