MicroRNA-133 controls cardiac hypertrophy

Alessandra Carè, Daniele Catalucci, Federica Felicetti, Désirée Bonci, Antonio Addario, Paolo Gallo, Marie Louise Bang, Patrizia Segnalini, Yusu Gu, Nancy D. Dalton, Leonardo Elia, Michael V G Latronico, Morten Høydal, Camillo Autore, Matteo A. Russo, Gerald W. Dorn, Øyvind Ellingsen, Pilar Ruiz-Lozano, Kirk L. Peterson, Carlo M. CroceCesare Peschle, Gianluigi Condorelli

Research output: Contribution to journalArticlepeer-review

Abstract

Growing evidence indicates that microRNAs (miRNAs or miRs) are involved in basic cell functions and oncogenesis. Here we report that miR-133 has a critical role in determining cardiomyocyte hypertrophy. We observed decreased expression of both miR-133 and miR-1, which belong to the same transcriptional unit, in mouse and human models of cardiac hypertrophy. In vitro overexpression of miR-133 or miR-1 inhibited cardiac hypertrophy. In contrast, suppression of miR-133 by 'decoy' sequences induced hypertrophy, which was more pronounced than that after stimulation with conventional inducers of hypertrophy. In vivo inhibition of miR-133 by a single infusion of an antagomir caused marked and sustained cardiac hypertrophy. We identified specific targets of miR-133: RhoA, a GDP-GTP exchange protein regulating cardiac hypertrophy; Cdc42, a signal transduction kinase implicated in hypertrophy; and Nelf-A/WHSC2, a nuclear factor involved in cardiogenesis. Our data show that miR-133, and possibly miR-1, are key regulators of cardiac hypertrophy, suggesting their therapeutic application in heart disease.

Original languageEnglish
Pages (from-to)613-618
Number of pages6
JournalNature Medicine
Volume13
Issue number5
DOIs
Publication statusPublished - May 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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