title: Endothelium-enriched microRNAs as diagnostic biomarkers for cardiac allograft vasculopathy.
abstract: BACKGROUND
  Cardiac allograft vasculopathy (CAV) is a limiting factor for the long-term survival of heart transplant recipients. Clinical decisions and care may be improved by the development of prediction models based on circulating biomarkers. The endothelium may play a central pathogenetic role in the development of CAV. We evaluated the hypothesis that endothelium-enriched microRNAs (miRNAs) discriminate between patients with and without CAV.
  
  
  METHODS
  This cross-sectional study recruited 52 patients undergoing coronary angiography between 5 and 15 years after heart transplantation. Circulating levels of endothelium-enriched miRNAs (miR-21-5p, miR-92a-3p, miR-92a-1-5p, miR-126-3p, and miR-126-5p) were quantified by real-time reverse transcription polymerase chain reaction. The discriminative ability of logistic regression models was evaluated using the concordance (C) statistic.
  
  
  RESULTS
  Median plasma levels of miR-210-5p, miR-92a-3p, miR-126-3p, and miR-126-5p were 1.82-fold (p = not significant), 1.87-fold (p < 0.05), 1.94-fold (p = 0.074), and 1.59-fold (p = 0.060) higher in patients with CAV than in patients without CAV. Recipient age (C statistic = 0.689; 95% confidence interval [CI], 0.537-0.842), and levels of serum creatinine (C statistic = 0.703; 95% CI, 0.552-0.854), miR-92a-3p (C statistic = 0.682; 95% CI, 0.533-0.831), and miR-126-5p (C statistic = 0.655; 95% CI, 0.502-0.807) predicted CAV status in univariable models. In multivariable logistic regression models with recipient age and creatinine as covariates, miR-126-5p (chi-square = 4.37(1), p = 0.037), miR-92a-3p (chi-square = 6.01(1), p = 0.014), and the combination of miR-126-5p and miR-92a-3p (chi-square = 8.16(2), p = 0.017) added significant information. The model with age, creatinine, miR-126-5p, and miR-92a-3p as covariables conferred good discrimination between patients without and with CAV (C statistic = 0.800; 95% CI, 0.674-0.926).
  
  
  CONCLUSIONS
  Endothelium-enriched miRNAs have diagnostic ability for CAV beyond clinical predictors.
authors.affiliation: Centre for Molecular and Vascular Biology.
authors.forename: Neha
authors.initials: N
authors.lastname: Singh
authors.affiliation: Centre for Molecular and Vascular Biology; Cardiology, Department of Cardiovascular Sciences, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Ward
authors.initials: W
authors.lastname: Heggermont
authors.affiliation: Interuniversity Institute for Biostatistics and statistical Bioinformatics, University of Leuven and University of Hasselt, Leuven, Belgium.
authors.forename: Steffen
authors.initials: S
authors.lastname: Fieuws
authors.affiliation: Cardiology, Department of Cardiovascular Sciences, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Vanhaecke
authors.affiliation: Cardiology, Department of Cardiovascular Sciences, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Van Cleemput
authors.affiliation: Centre for Molecular and Vascular Biology. Electronic address: bart.degeest@med.kuleuven.be.
authors.forename: Bart
authors.initials: B
authors.lastname: De Geest
mesh_terms: D000328:Adult; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012313:RNA
keywords: cardiac allograft vasculopathy; endothelium; heart transplantation; microRNA; prediction model