http://www.cnr.it/ontology/cnr/individuo/prodotto/ID285677

MicroRNA-133 modulates the b1-adrenergic receptor transduction cascade (Articolo in rivista)

Type

Articolo in rivista (Classe)
Prodotto della ricerca (Classe)

Label

MicroRNA-133 modulates the b1-adrenergic receptor transduction cascade (Articolo in rivista) (literal)

Anno

2014-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1161/CIRCRESAHA.115.303252 (literal)

Alternative label

Castaldi A.; Zaglia T.; Di Mauro V.; Carullo P.; Viggiani G.; Borile G.; Di Stefano B.; Schiattarella G.G.; Gualazzi M.G.; Elia L.; Stirparo G.G.; Colorito M.L.; Pironti G.; Kunderfranco P.; Esposito G.; Bang M.-L.; Mongillo M.; Condorelli G.; Catalucci D. (2014)
MicroRNA-133 modulates the b1-adrenergic receptor transduction cascade
in Circulation research
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Castaldi A.; Zaglia T.; Di Mauro V.; Carullo P.; Viggiani G.; Borile G.; Di Stefano B.; Schiattarella G.G.; Gualazzi M.G.; Elia L.; Stirparo G.G.; Colorito M.L.; Pironti G.; Kunderfranco P.; Esposito G.; Bang M.-L.; Mongillo M.; Condorelli G.; Catalucci D. (literal)

Pagina inizio

273 (literal)

Pagina fine

283 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

http://www.scopus.com/inward/record.url?eid=2-s2.0-84904040454&partnerID=q2rCbXpz (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

115 (literal)

Rivista

Circulation research (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

2 (literal)

Note

Scopu (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Humanitas Clinical and Research Center, Institute of Genetic and Biomedical Research, Milan Unit, via Manzoni 113, 20089 Rozzano, Milan, Italy; Multimedica, Milan, Italy; University of Milan Bicocca, Milan, Italy; Venetian Institute of Molecular Medicine, Padova, Italy; University of Padova, Padova, Italy; Institute of Genetic and Biomedical Research, Milan Unit, Milan, Italy; University Federico II, Naples, Italy; University of Milan, Milan, Italy; Duke University Medical Center, Durham, NC, United States; University of Palermo, Palermo, Italy (literal)

Titolo

MicroRNA-133 modulates the b1-adrenergic receptor transduction cascade (literal)

Abstract

RATIONALE:: The sympathetic nervous system plays a fundamental role in the regulation of myocardial function. During chronic pressure overload, overactivation of the sympathetic nervous system induces the release of catecholamines, which activate ?-adrenergic receptors in cardiomyocytes and lead to increased heart rate and cardiac contractility. However, chronic stimulation of ?-adrenergic receptors leads to impaired cardiac function, and ?-blockers are widely used as therapeutic agents for the treatment of cardiac disease. MicroRNA-133 (miR-133) is highly expressed in the myocardium and is involved in controlling cardiac function through regulation of messenger RNA translation/stability. OBJECTIVE:: To determine whether miR-133 affects ?-adrenergic receptor signaling during progression to heart failure. METHODS AND RESULTS:: Based on bioinformatic analysis, ?1-adrenergic receptor (?1AR) and other components of the ?1AR signal transduction cascade, including adenylate cyclase VI and the catalytic subunit of the cAMP-dependent protein kinase A, were predicted as direct targets of miR-133 and subsequently validated by experimental studies. Consistently, cAMP accumulation and activation of downstream targets were repressed by miR-133 overexpression in both neonatal and adult cardiomyocytes following selective ?1AR stimulation. Furthermore, gain-of-function and loss-of-function studies of miR-133 revealed its role in counteracting the deleterious apoptotic effects caused by chronic ?1AR stimulation. This was confirmed in vivo using a novel cardiac-specific TetON-miR-133 inducible transgenic mouse model. When subjected to transaortic constriction, TetON-miR-133 inducible transgenic mice maintained cardiac performance and showed attenuated apoptosis and reduced fibrosis compared with control mice. CONCLUSIONS:: miR-133 controls multiple components of the ?1AR transduction cascade and is cardioprotective during heart failure. © 2014 American Heart Association, Inc. (literal)

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