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Letter


Nature Medicine 13, 613 - 618 (2007)
Published online: 29 April 2007 | doi:10.1038/nm1582

MicroRNA-133 controls cardiac hypertrophy

Alessandra Carè1,11, Daniele Catalucci2,3,11, Federica Felicetti1, Désirée Bonci1, Antonio Addario1, Paolo Gallo3,4, Marie-Louise Bang2,3, Patrizia Segnalini1, Yusu Gu2, Nancy D Dalton2, Leonardo Elia2, Michael V G Latronico3,4, Morten Høydal5, Camillo Autore6, Matteo A Russo7, Gerald W Dorn II8, Øyvind Ellingsen5, Pilar Ruiz-Lozano9, Kirk L Peterson2, Carlo M Croce10, Cesare Peschle1,11 & Gianluigi Condorelli2,3,11


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.


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