@article{10902/1127,
year = {2012},
month = {8},
url = {http://hdl.handle.net/10902/1127},
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 wasperformed in myocardial sections. Results: The myocardial and plasma levels of miR-21 were significantly higher in the AS patients compared with 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-β 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.},
organization = {This work was supported by the Instituto de Salud Carlos III [PS09/01097], Ministerio de Ciencia e Innovación (SAF2010-16894), Fundación Marqués de Valdecilla Universidad de Cantabria [FMV-UC 09/01], and Instituto de Formación e Investigación Marqués de Valdecilla [FMV-API 10/20]},
publisher = {Elsevier},
publisher = {International Journal of Cardiology, 2013, 167(6), 2875-81},
title = {Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients},
author = {Villar Ramos, Ana Victoria and García López, Raquel and Merino Fernández, David and Llano Cardenal, Miguel and Cobo Belaustegui, Manuel and Montalvo Silva, Cecilia de and Martín Durán, Rafael and Hurlé González, María Amor and Nistal Herrera, Juan Francisco},
}