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.