{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:41:55Z","timestamp":1792708915637,"version":"4.5.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Anthracycline chemotherapeutics, such as doxorubicin, are used widely in the treatment of numerous malignancies. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that often presents as heart failure due to dilated cardiomyopathy years after anthracycline exposure. Recent data from animal studies indicate that anthracyclines cause cardiac atrophy. The timing of onset and underlying mechanisms are not well defined, and the relevance of these findings to human disease is unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p>\n              Wild-type mice were sacrificed 1 week after intraperitoneal administration of doxorubicin (1\u201325 mg\/kg), revealing a dose-dependent decrease in cardiac mass (\n              <jats:italic>R<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\n              =0.64;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001) and a significant decrease in cardiomyocyte cross-sectional area (336\u00b129 versus 188\u00b114 \u00b5m\n              <jats:sup>2<\/jats:sup>\n              ;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001). Myocardial tissue analysis identified a dose-dependent upregulation of the ubiquitin ligase, MuRF1 (muscle ring finger-1; R\n              <jats:sup>2<\/jats:sup>\n              =0.91;\n              <jats:italic>P<\/jats:italic>\n              =0.003) and a molecular profile of muscle atrophy. To investigate the determinants of doxorubicin-induced cardiac atrophy, we administered doxorubicin 20 mg\/kg to mice lacking MuRF1 (MuRF1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ) and wild-type littermates. MuRF1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice were protected from cardiac atrophy and exhibited no reduction in contractile function. To explore the clinical relevance of these findings, we analyzed cardiac magnetic resonance imaging data from 70 patients in the DETECT-1 cohort and found that anthracycline exposure was associated with decreased cardiac mass evident within 1 month and persisting to 6 months after initiation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Doxorubicin causes a subacute decrease in cardiac mass in both mice and humans. In mice, doxorubicin-induced cardiac atrophy is dependent on MuRF1. These findings suggest that therapies directed at preventing or reversing cardiac atrophy might preserve the cardiac function of cancer patients receiving anthracyclines.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.118.005234","type":"journal-article","created":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T09:00:36Z","timestamp":1552640436000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":131,"title":["Doxorubicin Exposure Causes Subacute Cardiac Atrophy Dependent on the Striated Muscle\u2013Specific Ubiquitin Ligase MuRF1"],"prefix":"10.1161","volume":"12","author":[{"given":"Monte S.","family":"Willis","sequence":"first","affiliation":[{"name":"Indiana Center for Musculoskeletal Health, Department of Pathology and Laboratory Medicine, and Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis (M.S.W)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Traci L.","family":"Parry","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine (T.L.P.), University of North Carolina School of Medicine, Chapel Hill."},{"name":"McAllister Heart Institute (T.L.P., D.I.B., R.I.M., W.H., B.C.J.), University of North Carolina School of Medicine, Chapel Hill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David I.","family":"Brown","sequence":"additional","affiliation":[{"name":"McAllister Heart Institute (T.L.P., D.I.B., R.I.M., W.H., B.C.J.), University of North Carolina School of Medicine, Chapel Hill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto I.","family":"Mota","sequence":"additional","affiliation":[{"name":"McAllister Heart Institute (T.L.P., D.I.B., R.I.M., W.H., B.C.J.), University of North Carolina School of Medicine, Chapel Hill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"McAllister Heart Institute (T.L.P., D.I.B., R.I.M., W.H., B.C.J.), University of North Carolina School of Medicine, Chapel Hill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Youn","family":"Beak","sequence":"additional","affiliation":[{"name":"Indiana Center for Musculoskeletal Health, Department of Pathology and Laboratory Medicine, and Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis (M.S.W)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sola","sequence":"additional","affiliation":[{"name":"Indiana Center for Musculoskeletal Health, Department of Pathology and Laboratory Medicine, and Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis (M.S.W)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Indiana Center for Musculoskeletal Health, Department of Pathology and Laboratory Medicine, and Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis (M.S.W)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean T","family":"Hicks","sequence":"additional","affiliation":[{"name":"Indiana Center for Musculoskeletal Health, Department of Pathology and Laboratory Medicine, and Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis (M.S.W)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa C.","family":"Caughey","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine (M.C.C., B.C.J.), University of North Carolina School of Medicine, Chapel Hill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Ralph B.","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"Department of Biostatistical Sciences (R.B.D.), Wake Forest Health Sciences."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Jordan","sequence":"additional","affiliation":[{"name":"Section on Cardiovascular Medicine (J.J., W.G.H.), Wake Forest Health Sciences."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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