title: Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients.
abstract: BACKGROUND
  Various human cardiovascular pathophysiological conditions associate aberrant expression of microRNAs (miRNAs) and circulating miRNAs are emerging as promising biomarkers. In mice, myocardial miR-21 overexpression is related to cardiac fibrosis elicited by pressure overload. This study was designed to determine the role of myocardial and plasmatic miR-21 in the maladaptive remodeling of the extracellular matrix induced by pressure overload in aortic stenosis (AS) patients and the clinical value of miR-21 as a biomarker for pathological myocardial fibrosis.
  
  
  METHODS
  In left ventricular biopsies from 75 AS patients and 32 surgical controls, we quantified the myocardial transcript levels of miR-21, miR-21-targets and ECM- and TGF-β-signaling-related elements. miR-21 plasma levels were determined in 25 healthy volunteers and in AS patients. In situ hybridization of miR-21 was performed in myocardial sections.
  
  
  RESULTS
  The myocardial and plasma levels of miR-21 were significantly higher in the AS patients compared with the controls and correlated directly with the echocardiographic mean transvalvular gradients. miR-21 overexpression was confined to interstitial cells and absent in cardiomyocytes. Using bootstrap validated multiple linear regression, the variance in myocardial collagen expression was predicted by myocardial miR-21 (70% of collagen variance) or plasma miR-21 (52% of collagen variance), together with the miR-21 targets RECK and PDCD4, and effectors of TGF-ß signaling.
  
  
  CONCLUSIONS
  Our results support the role of miR-21 as a regulator of the fibrotic process that occurs in response to pressure overload in AS patients and underscore the value of circulating miR-21 as a biomarker for myocardial fibrosis.
authors.affiliation: Universidad de Cantabria, Santander, Spain.
authors.forename: Ana V
authors.initials: AV
authors.lastname: Villar
authors.forename: Raquel
authors.initials: R
authors.lastname: García
authors.forename: David
authors.initials: D
authors.lastname: Merino
authors.forename: Miguel
authors.initials: M
authors.lastname: Llano
authors.forename: Manuel
authors.initials: M
authors.lastname: Cobo
authors.forename: Cecilia
authors.initials: C
authors.lastname: Montalvo
authors.forename: Rafael
authors.initials: R
authors.lastname: Martín-Durán
authors.forename: María A
authors.initials: MA
authors.lastname: Hurlé
authors.forename: J Francisco
authors.initials: JF
authors.lastname: Nistal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C524940:MIRN21 microRNA, human; D035683:MicroRNAs