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

Eva Van Rooij, Lillian B. Sutherland, Ning Liu, Andrew H. Williams, John McAnally, Robert D. Gerard, James A. Richardson, Eric N. Olson

Research output: Contribution to journalArticlepeer-review

1166 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)18255-18260
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number48
DOIs
StatePublished - Nov 28 2006

Keywords

  • Calcineurin
  • Cardiomyocytes
  • Myosin heavy chain
  • Thoracic aortic banding

ASJC Scopus subject areas

  • General

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