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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-?-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.

 Autoría: Villar A., García R., Merino D., Llano M., Cobo M., Montalvo C., Martín-Durán R., Hurlé M., Nistal J.,

 Fuente: International Journal of Cardiology, 2013, 167(6), 2875-81

 Editorial: Elsevier

 Año de publicación: 2013

 Nº de páginas: 7

 Tipo de publicación: Artículo de Revista

 DOI: 10.1016/j.ijcard.2012.07.021

 ISSN: 0167-5273,1874-1754

 Proyecto español: SAF2010-16894

 Url de la publicación: http://dx.doi.org/10.1016/j.ijcard.2012.07.021