TY - JOUR
T1 - MicroRNA-133 controls cardiac hypertrophy
AU - Carè, Alessandra
AU - Catalucci, Daniele
AU - Felicetti, Federica
AU - Bonci, Désirée
AU - Addario, Antonio
AU - Gallo, Paolo
AU - Bang, Marie Louise
AU - Segnalini, Patrizia
AU - Gu, Yusu
AU - Dalton, Nancy D.
AU - Elia, Leonardo
AU - Latronico, Michael V.G.
AU - Høydal, Morten
AU - Autore, Camillo
AU - Russo, Matteo A.
AU - Dorn, Gerald W.
AU - Ellingsen, Øyvind
AU - Ruiz-Lozano, Pilar
AU - Peterson, Kirk L.
AU - Croce, Carlo M.
AU - Peschle, Cesare
AU - Condorelli, Gianluigi
N1 - Funding Information:
We thank M. Blasi, M. Fontana and V. Michetti for editorial assistance, and G. Loreto for graphics. This work was supported by grants from the US National Institutes of Health (HL078797-01A1 to G.C., HLO65484 to P.R.-L. and 1R01HL63168 to C.P.), the Marie Curie Outgoing Fellowship 6th European Framework Programme (D.C.), EUGeneHeart (LSHM-CT-2005-018833 to G.C.), the Italian Ministry of Scientific Research (G.C. and C.P.), the Italian Ministry of Health (C.P. and G.C.) and the Italy-USA miR Oncology Program, Istituto Superiore di Sanità, Rome (C.P.).
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34249279050&partnerID=8YFLogxK
U2 - 10.1038/nm1582
DO - 10.1038/nm1582
M3 - Article
C2 - 17468766
AN - SCOPUS:34249279050
SN - 1078-8956
VL - 13
SP - 613
EP - 618
JO - Nature Medicine
JF - Nature Medicine
IS - 5
ER -