A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure.

Abstract:

:Diverse forms of injury and stress evoke a hypertrophic growth response in adult cardiac myocytes, which is characterized by an increase in cell size, enhanced protein synthesis, assembly of sarcomeres, and reactivation of fetal genes, often culminating in heart failure and sudden death. Given the emerging roles of microRNAs (miRNAs) in modulation of cellular phenotypes, we searched for miRNAs that were regulated during cardiac hypertrophy and heart failure. We describe >12 miRNAs that are up- or down-regulated in cardiac tissue from mice in response to transverse aortic constriction or expression of activated calcineurin, stimuli that induce pathological cardiac remodeling. Many of these miRNAs were similarly regulated in failing human hearts. Forced overexpression of stress-inducible miRNAs was sufficient to induce hypertrophy in cultured cardiomyocytes. Similarly, cardiac overexpression of miR-195, which was up-regulated during cardiac hypertrophy, resulted in pathological cardiac growth and heart failure in transgenic mice. These findings reveal an important role for specific miRNAs in the control of hypertrophic growth and chamber remodeling of the heart in response to pathological signaling and point to miRNAs as potential therapeutic targets in heart disease.

authors

van Rooij E,Sutherland LB,Liu N,Williams AH,McAnally J,Gerard RD,Richardson JA,Olson EN

doi

10.1073/pnas.0608791103

subject

Has Abstract

pub_date

2006-11-28 00:00:00

pages

18255-60

issue

48

eissn

0027-8424

issn

1091-6490

pii

0608791103

journal_volume

103

pub_type

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