title: Circulating microRNAs as biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Circulating microRNAs may represent novel markers for cardiovascular diseases. We evaluated whether circulating miRNAs served as potential biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM).
  
  
  METHODS
  Cardiac magnetic resonance imaging with postcontrast T1 mapping was performed to non-invasively quantify diffuse myocardial fibrosis in HCM patients who were classified into two groups (T1 < 470 ms or T1 ≥ 470 ms, as likely or unlikely to have diffuse fibrosis, respectively). First, we screened 84 miRNAs using human serum/plasma miRNA array on plasma of 8 HCM patients (4/group based on T1 time) and 4 healthy controls. From the results of this initial array, 16 miRNAs were selected based on their fold changes and relevance to myocardial fibrosis for further validation by Taqman real-time PCR in 55 HCM patients.
  
  
  RESULTS
  Among the 16 miRNAs, the expression of miR-96-5p and miR-373-3p was low. The remaining 14 (miR-18a-5p, miR-146a-5p, miR-30d-5p, miR-17-5p, miR-200a-3p, miR-19b-3p, miR-21-5p, miR-193-5p, miR-10b-5p, miR-15a-5p, miR-192-5p, miR-296-5p, miR-29a-3p, and miR-133a-3p) were upregulated in HCM patients with T1 < 470 ms compared with those with T1 ≥ 470 ms, and 11 (except miR-192-5p, miR-296-5p and miR-133a-3p) were significantly inversely correlated with postcontrast T1 values. Individual miRNA had moderate diagnostic value for diffuse myocardial fibrosis (AUC: 0.663-0.742), but the diagnostic value was greatly improved (AUC: 0.87) for a combination of 8 miRNAs. In comparison, circulating markers of collagen turnover did not have predictive values for diffuse myocardial fibrosis.
  
  
  CONCLUSIONS
  These findings suggest that circulating miRNAs provide attractive candidates as putative biomarkers for diffuse myocardial fibrosis in HCM.
authors.affiliation: Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, 3004, Australia. kfanglu@bakeridi.edu.au.
authors.forename: Lu
authors.initials: L
authors.lastname: Fang
authors.affiliation: Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, 3004, Australia. A.Ellims@alfred.org.au.|Department of Cardiovascular Medicine, Alfred Heart Centre, The Alfred Hospital, 55 Commercial Road, Melbourne, VIC, 3004, Australia. A.Ellims@alfred.org.au.
authors.forename: Andris H
authors.initials: AH
authors.lastname: Ellims
authors.affiliation: Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, 3004, Australia. Shirley.Moore@bakeridi.edu.au.
authors.forename: Xiao-lei
authors.initials: XL
authors.lastname: Moore
authors.affiliation: Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, 3004, Australia. DWHITE@research.bwh.harvard.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: White
authors.affiliation: Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, 3004, Australia. A.Taylor@alfred.org.au.|Department of Cardiovascular Medicine, Alfred Heart Centre, The Alfred Hospital, 55 Commercial Road, Melbourne, VIC, 3004, Australia. A.Taylor@alfred.org.au.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Taylor
authors.affiliation: Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, 3004, Australia. Jaye.Chin-Dusting@bakeridi.edu.au.
authors.forename: Jaye
authors.initials: J
authors.lastname: Chin-Dusting
authors.affiliation: Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, 3004, Australia. a.dart@alfred.org.au.|Department of Cardiovascular Medicine, Alfred Heart Centre, The Alfred Hospital, 55 Commercial Road, Melbourne, VIC, 3004, Australia. a.dart@alfred.org.au.|Monash University, Melbourne, Australia. a.dart@alfred.org.au.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Dart
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D004452:Echocardiography; D005260:Female; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D012313:RNA / Q000032:analysis; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012313:RNA