title: MicroRNA 628-5p as a Novel Biomarker for Cardiac Allograft Vasculopathy.
abstract: BACKGROUND
  Cardiac allograft vasculopathy (CAV) remains the leading cause of morbidity and mortality after orthotopic heart transplantation (OHT). Because of its clinically silent progression and lack of symptoms, detection is often difficult and invasive coronary angiography is performed routinely. To date, there are no established noninvasive biomarkers available for prediction of CAV in transplanted patients.MicroRNAs (miRNAs) are highly conserved, small noncoding RNA molecules that negatively regulate gene expression. As they are detectable in peripheral blood, recent studies have suggested miRNAs as biomarkers for various cardiovascular diseases. Thus, we hypothesized that circulating miRNAs may serve as noninvasive biomarkers for CAV.
  
  
  METHODS
  To determine the regulation of circulating miRNAs, we performed miRNA profiling studies in plasma samples of OHT patients with confirmed high-degree CAV and a matched control group consisting of patients without any signs of CAV at least 5 years after OHT. Candidate miRNAs were verified by quantitative reverse transcriptase polymerase chain reaction.
  
  
  RESULTS
  Microarray analysis revealed 5 candidate miRNAs (miR-34a, miR-98, miR-155, miR-204, miR-628-5p) that were differentially regulated in plasma samples of patients with CAV and therefore were selected for verification by quantitative reverse transcriptase polymerase chain reaction. In CAV patients, plasma levels of miR-628-5p and miR-155 were significantly increased (P = 0.001 and P = 0.028, respectively). A miR628-5p value above 1.336 was able to predict CAV with a sensitivity of 72% and a specificity of 83%.
  
  
  CONCLUSIONS
  For the first time, the present study identifies the circulating miRNA miR-628-5p as a novel potential biomarker of CAV in patients after OHT.
authors.affiliation: 1 Hannover Medical School (MHH), Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover, Germany. 2 Hannover Medical School (MHH), Department of Cardiology and Angiology, Hannover, Germany. 3 Hannover Medical School (MHH), Integrated Research and Treatment Center Transplantation, Hannover, Germany. 4 Hannover Medical School (MHH), Institute of Molecular and Translational Therapeutic Strategies, Hannover, Germany. 5 Hannover Medical School (MHH), REBIRTH Cluster of Excellence, Hannover, Germany. 6 Imperial College of Medicine London, National Heart and Lung Institute, London, United Kingdom.
authors.forename: Anneke
authors.initials: A
authors.lastname: Neumann
authors.forename: L Christian
authors.initials: LC
authors.lastname: Napp
authors.forename: Jan A
authors.initials: JA
authors.lastname: Kleeberger
authors.forename: Nils
authors.initials: N
authors.lastname: Benecke
authors.forename: Angelika
authors.initials: A
authors.lastname: Pfanne
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
authors.forename: Christoph
authors.initials: C
authors.lastname: Bara
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D019540:Area Under Curve; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C000589022:MIRN628 microRNA, human; D035683:MicroRNAs