{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:46:04Z","timestamp":1791326764720,"version":"4.3.1"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>Cardiac myocyte hypertrophy is regulated by an extensive intracellular signal transduction network. In vitro evidence suggests that the scaffold protein muscle A-kinase anchoring protein \u03b2 (mAKAP\u03b2) serves as a nodal organizer of hypertrophic signaling. However, the relevance of mAKAP\u03b2 signalosomes to pathological remodeling and heart failure in vivo remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Using conditional, cardiac myocyte\u2013specific gene deletion, we now demonstrate that mAKAP\u03b2 expression in mice is important for the cardiac hypertrophy induced by pressure overload and catecholamine toxicity. mAKAP\u03b2 targeting prevented the development of heart failure associated with long-term transverse aortic constriction, conferring a survival benefit. In contrast to 29% of control mice (n=24), only 6% of mAKAP\u03b2 knockout mice (n=31) died in the 16 weeks of pressure overload (\n                      <jats:italic>P<\/jats:italic>\n                      =0.02). Accordingly, mAKAP\u03b2 knockout inhibited myocardial apoptosis and the development of interstitial fibrosis, left atrial hypertrophy, and pulmonary edema. This improvement in cardiac status correlated with the attenuated activation of signaling pathways coordinated by the mAKAP\u03b2 scaffold, including the decreased phosphorylation of protein kinase D1 and histone deacetylase 4 that we reveal to participate in a new mAKAP signaling module. Furthermore, mAKAP\u03b2 knockout inhibited pathological gene expression directed by myocyte-enhancer factor-2 and nuclear factor of activated T-cell transcription factors that associate with the scaffold.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>mAKAP\u03b2 orchestrates signaling that regulates pathological cardiac remodeling in mice. Targeting of the underlying physical architecture of signaling networks, including mAKAP\u03b2 signalosome formation, may constitute an effective therapeutic strategy for the prevention and treatment of pathological remodeling and heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.114.001266","type":"journal-article","created":{"date-parts":[[2014,5,8]],"date-time":"2014-05-08T22:53:58Z","timestamp":1399589638000},"page":"663-672","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":62,"title":["The Scaffold Protein Muscle A-Kinase Anchoring Protein \u03b2 Orchestrates Cardiac Myocyte Hypertrophic Signaling Required for the Development of Heart Failure"],"prefix":"10.1161","volume":"7","author":[{"given":"Michael D.","family":"Kritzer","sequence":"first","affiliation":[{"name":"From the Cardiac Signal Transduction and Cellular Biology Laboratory, Interdisciplinary Stem Cell Institute, Departments of Pediatrics and Medicine, Leonard M. Miller School of Medicine, University of Miami, FL (M.D.K., J.L., C.L.P., M.G., H.T., J.D., M.S.K.); and Calhoun Center for Cardiology, University of Connecticut Health Center, Farmington (K.D.-K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinliang","family":"Li","sequence":"additional","affiliation":[{"name":"From the Cardiac Signal Transduction and Cellular Biology Laboratory, Interdisciplinary Stem Cell Institute, Departments of Pediatrics and Medicine, Leonard M. Miller School of Medicine, University of Miami, FL (M.D.K., J.L., C.L.P., M.G., H.T., J.D., M.S.K.); and Calhoun Center for Cardiology, University of Connecticut Health Center, Farmington (K.D.-K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine L.","family":"Passariello","sequence":"additional","affiliation":[{"name":"From the Cardiac Signal Transduction and Cellular Biology Laboratory, Interdisciplinary Stem Cell Institute, Departments of Pediatrics and Medicine, Leonard M. Miller School of Medicine, University of Miami, FL (M.D.K., J.L., C.L.P., M.G., H.T., J.D., M.S.K.); and Calhoun Center for Cardiology, University of Connecticut Health Center, Farmington (K.D.-K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Gayanilo","sequence":"additional","affiliation":[{"name":"From the Cardiac Signal Transduction and Cellular Biology Laboratory, Interdisciplinary Stem Cell Institute, Departments of Pediatrics and Medicine, Leonard M. Miller School of Medicine, University of Miami, FL (M.D.K., J.L., C.L.P., M.G., H.T., J.D., M.S.K.); and Calhoun Center for Cardiology, University of Connecticut Health Center, Farmington (K.D.-K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hrishikesh","family":"Thakur","sequence":"additional","affiliation":[{"name":"From the Cardiac Signal Transduction and Cellular Biology Laboratory, Interdisciplinary Stem Cell Institute, Departments of Pediatrics and Medicine, Leonard M. Miller School of Medicine, University of Miami, FL (M.D.K., J.L., C.L.P., M.G., H.T., J.D., M.S.K.); and Calhoun Center for Cardiology, University of Connecticut Health Center, Farmington (K.D.-K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Dayan","sequence":"additional","affiliation":[{"name":"From the Cardiac Signal Transduction and Cellular Biology Laboratory, Interdisciplinary Stem Cell Institute, Departments of Pediatrics and Medicine, Leonard M. Miller School of Medicine, University of Miami, FL (M.D.K., J.L., C.L.P., M.G., H.T., J.D., M.S.K.); and Calhoun Center for Cardiology, University of Connecticut Health Center, Farmington (K.D.-K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Dodge-Kafka","sequence":"additional","affiliation":[{"name":"From the Cardiac Signal Transduction and Cellular Biology Laboratory, Interdisciplinary Stem Cell Institute, Departments of Pediatrics and Medicine, Leonard M. Miller School of Medicine, University of Miami, FL (M.D.K., J.L., C.L.P., M.G., H.T., J.D., M.S.K.); and Calhoun Center for Cardiology, University of Connecticut Health Center, Farmington (K.D.-K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Kapiloff","sequence":"additional","affiliation":[{"name":"From the Cardiac Signal Transduction and Cellular Biology Laboratory, Interdisciplinary Stem Cell Institute, Departments of Pediatrics and Medicine, Leonard M. Miller School of Medicine, University of Miami, FL (M.D.K., J.L., C.L.P., M.G., H.T., J.D., M.S.K.); and Calhoun Center for Cardiology, University of Connecticut Health Center, Farmington 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