Document Detail

Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients.
MedLine Citation:
PMID:  22882958     Owner:  NLM     Status:  Publisher    
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.
Ana V Villar; Raquel García; David Merino; Miguel Llano; Manuel Cobo; Cecilia Montalvo; Rafael Martín-Durán; María A Hurlé; J Francisco Nistal
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-8
Journal Detail:
Title:  International journal of cardiology     Volume:  -     ISSN:  1874-1754     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Universidad de Cantabria, Santander, Spain; Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Spain.
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