title: Micro-RNA-126 Reduces the Blood Thrombogenicity in Diabetes Mellitus via Targeting of Tissue Factor.
abstract: Diabetes mellitus involves vascular inflammatory processes and is a main contributor to cardiovascular mortality. Notably, heightened levels of circulating tissue factor (TF) account for the increased thrombogenicity and put those patients at risk for thromboembolic events. Here, we sought to investigate the role of micro-RNA (miR)-driven TF expression and thrombogenicity in diabetes mellitus.
  
  
  
  Plasma samples of patients with diabetes mellitus were analyzed for TF protein and activity as well as miR-126 expression before and after optimization of the antidiabetic treatment. We found low miR-126 levels to be associated with markedly increased TF protein and TF-mediated thrombogenicity. Reduced miR-126 expression was accompanied by increased vascular inflammation as evident from the levels of vascular adhesion molecule-1 and fibrinogen, as well as leukocyte counts. With optimization of the antidiabetic treatment miR-126 levels increased and thrombogenicity was reduced. Using a luciferase reporter system, we demonstrated miR-126 to directly bind to the F3-3'-untranslated region, thereby reducing TF expression both on mRNA and on protein levels in human microvascular endothelial cells as well as TF mRNA and activity in monocytes.
  
  
  
  Circulating miR-126 exhibits antithrombotic properties via regulating post-transcriptional TF expression, thereby impacting the hemostatic balance of the vasculature in diabetes mellitus.
authors.affiliation: From the Charité Centrum 11, Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany; Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany; and Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Witkowski
authors.affiliation: From the Charité Centrum 11, Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany; Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany; and Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Weithauser
authors.affiliation: From the Charité Centrum 11, Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany; Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany; and Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen, Germany.
authors.forename: Termeh
authors.initials: T
authors.lastname: Tabaraie
authors.affiliation: From the Charité Centrum 11, Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany; Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany; and Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Steffens
authors.affiliation: From the Charité Centrum 11, Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany; Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany; and Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen, Germany.
authors.forename: Nicolle
authors.initials: N
authors.lastname: Kränkel
authors.affiliation: From the Charité Centrum 11, Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany; Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany; and Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Witkowski
authors.affiliation: From the Charité Centrum 11, Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany; Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany; and Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Stratmann
authors.affiliation: From the Charité Centrum 11, Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany; Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany; and Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen, Germany.
authors.forename: Diethelm
authors.initials: D
authors.lastname: Tschoepe
authors.affiliation: From the Charité Centrum 11, Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany; Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany; and Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.affiliation: From the Charité Centrum 11, Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany; Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany; and Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen, Germany. ursula.rauch@charite.de.
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauch-Kroehnert
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D001665:Binding Sites; D002460:Cell Line; D003920:Diabetes Mellitus / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D034622:RNA Interference; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood* / Q000235:genetics / Q000517:prevention & control; D013997:Time Factors; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D020413:3' Untranslated Regions; D007004:Hypoglycemic Agents; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D019010:Vascular Cell Adhesion Molecule-1; D005340:Fibrinogen; D013925:Thromboplastin
keywords: diabetes mellitus; endothelial cells; monocytes; thromboplastin; untranslated regions