{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:24:42Z","timestamp":1791296682586,"version":"4.1.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2014,7,7]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale<\/jats:underline>\n                      :\n                    <\/jats:title>\n                    <jats:p>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 \u03b2-adrenergic receptors in cardiomyocytes and lead to increased heart rate and cardiac contractility. However, chronic stimulation of \u03b2-adrenergic receptors leads to impaired cardiac function, and \u03b2-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective<\/jats:underline>\n                      :\n                    <\/jats:title>\n                    <jats:p>To determine whether miR-133 affects \u03b2-adrenergic receptor signaling during progression to heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results<\/jats:underline>\n                      :\n                    <\/jats:title>\n                    <jats:p>\n                      Based on bioinformatic analysis, \u03b2\n                      <jats:sub>1<\/jats:sub>\n                      -adrenergic receptor (\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      AR) and other components of the \u03b2\n                      <jats:sub>1<\/jats:sub>\n                      AR 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 \u03b2\n                      <jats:sub>1<\/jats:sub>\n                      AR 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 \u03b2\n                      <jats:sub>1<\/jats:sub>\n                      AR 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions<\/jats:underline>\n                      :\n                    <\/jats:title>\n                    <jats:p>\n                      miR-133 controls multiple components of the \u03b2\n                      <jats:sub>1<\/jats:sub>\n                      AR transduction cascade and is cardioprotective during heart failure.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.115.303252","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T21:53:05Z","timestamp":1399499585000},"page":"273-283","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":113,"title":["MicroRNA-133 Modulates the \u03b2\n                    <sub>1<\/sub>\n                    -Adrenergic Receptor Transduction Cascade"],"prefix":"10.1161","volume":"115","author":[{"given":"Alessandra","family":"Castaldi","sequence":"first","affiliation":[{"name":"From the Humanitas Clinical and Research Center, Rozzano, Milan, Italy (A.C., V.D.M., P.C., G.V., M.G.G., G.G.S., P.K., M.-L.B., G.C., D.C.); Multimedica, Milan, Italy (L.E.); University of Milan Bicocca, Milan, Italy (A.C.); Venetian Institute of Molecular Medicine, Padova, Italy (T.Z., G.B., M.M.); University of Padova, Padova, Italy (T.Z., G.B., M.M.); Institute of Genetic and Biomedical Research\u2013Milan Unit, Milan, Italy (P.C., M.-L.B., G.C., D.C.); University \u201cFederico II,\u201d Naples, Italy (G.G.S...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Zaglia","sequence":"additional","affiliation":[{"name":"From the Humanitas Clinical and Research Center, Rozzano, Milan, Italy (A.C., V.D.M., P.C., G.V., M.G.G., G.G.S., P.K., M.-L.B., G.C., D.C.); Multimedica, Milan, Italy (L.E.); University of Milan Bicocca, Milan, Italy (A.C.); Venetian Institute of Molecular Medicine, Padova, Italy (T.Z., G.B., M.M.); University of Padova, Padova, Italy (T.Z., G.B., M.M.); Institute of Genetic and Biomedical Research\u2013Milan Unit, Milan, Italy (P.C., M.-L.B., G.C., D.C.); University \u201cFederico II,\u201d Naples, Italy (G.G.S...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Di Mauro","sequence":"additional","affiliation":[{"name":"From the Humanitas Clinical and Research Center, Rozzano, Milan, Italy (A.C., V.D.M., P.C., G.V., M.G.G., G.G.S., P.K., M.-L.B., G.C., D.C.); Multimedica, Milan, Italy (L.E.); University of Milan Bicocca, Milan, Italy (A.C.); Venetian Institute of Molecular Medicine, Padova, Italy (T.Z., G.B., M.M.); University of Padova, Padova, Italy (T.Z., G.B., M.M.); Institute of Genetic and Biomedical Research\u2013Milan Unit, Milan, Italy (P.C., M.-L.B., G.C., D.C.); University \u201cFederico II,\u201d Naples, Italy (G.G.S...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Carullo","sequence":"additional","affiliation":[{"name":"From the Humanitas Clinical and Research Center, Rozzano, Milan, Italy (A.C., V.D.M., P.C., G.V., M.G.G., G.G.S., P.K., M.-L.B., G.C., D.C.); Multimedica, Milan, Italy (L.E.); University of Milan Bicocca, Milan, Italy (A.C.); Venetian Institute of Molecular Medicine, Padova, Italy (T.Z., G.B., M.M.); University of Padova, Padova, Italy (T.Z., G.B., M.M.); Institute of Genetic and Biomedical Research\u2013Milan Unit, Milan, Italy (P.C., M.-L.B., G.C., D.C.); University \u201cFederico II,\u201d Naples, Italy (G.G.S...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Viggiani","sequence":"additional","affiliation":[{"name":"From the Humanitas Clinical and Research Center, Rozzano, Milan, Italy (A.C., V.D.M., P.C., G.V., M.G.G., G.G.S., P.K., M.-L.B., G.C., D.C.); Multimedica, Milan, Italy (L.E.); University of Milan Bicocca, Milan, Italy (A.C.); Venetian Institute of Molecular Medicine, Padova, Italy (T.Z., G.B., M.M.); University of Padova, Padova, Italy (T.Z., G.B., M.M.); Institute of Genetic and Biomedical Research\u2013Milan Unit, Milan, Italy (P.C., M.-L.B., G.C., D.C.); University \u201cFederico II,\u201d Naples, Italy (G.G.S...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Borile","sequence":"additional","affiliation":[{"name":"From the Humanitas Clinical and Research Center, Rozzano, Milan, Italy (A.C., V.D.M., P.C., G.V., M.G.G., G.G.S., P.K., M.-L.B., G.C., D.C.); Multimedica, Milan, Italy (L.E.); University of Milan Bicocca, Milan, Italy (A.C.); Venetian Institute of Molecular Medicine, Padova, Italy (T.Z., G.B., M.M.); University of Padova, Padova, Italy (T.Z., G.B., M.M.); Institute of Genetic and Biomedical Research\u2013Milan Unit, Milan, Italy (P.C., M.-L.B., G.C., D.C.); University \u201cFederico II,\u201d Naples, Italy (G.G.S...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Di Stefano","sequence":"additional","affiliation":[{"name":"From the Humanitas Clinical and Research Center, Rozzano, Milan, Italy (A.C., V.D.M., P.C., G.V., M.G.G., G.G.S., P.K., M.-L.B., G.C., D.C.); 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