{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:21:29Z","timestamp":1792167689221,"version":"4.4.0"},"reference-count":54,"publisher":"American Society for Clinical Investigation","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,5,5]]},"abstract":"<jats:p>\n                    Dilated cardiomyopathy (DCM) is defined by progressive functional and structural changes. We performed RNA-seq at different stages of disease to define molecular signaling in the progression from pre-DCM hearts to DCM and overt heart failure (HF) using a genetic model of DCM (phospholamban missense mutation, PLN\n                    <jats:sup>R9C\/+<\/jats:sup>\n                    ). Pre-DCM hearts were phenotypically normal yet displayed proliferation of nonmyocytes (59% relative increase vs. WT,\n                    <jats:italic>P<\/jats:italic>\n                    = 8 \u00d7 10\n                    <jats:sup>\u20134<\/jats:sup>\n                    ) and activation of proinflammatory signaling with notable cardiomyocyte-specific induction of a subset of profibrotic cytokines including TGF\u03b22 and TGF\u03b23. These changes progressed through DCM and HF, resulting in substantial fibrosis (17.6% of left ventricle [LV] vs. WT,\n                    <jats:italic>P<\/jats:italic>\n                    = 6 \u00d7 10\n                    <jats:sup>\u201333<\/jats:sup>\n                    ). Cardiomyocytes displayed a marked shift in metabolic gene transcription: downregulation of aerobic respiration and subsequent upregulation of glucose utilization, changes coincident with attenuated expression of PPAR\u03b1 and PPAR\u03b3 coactivators -1\u03b1 (PGC1\u03b1) and -1\u03b2, and increased expression of the metabolic regulator T-box transcription factor 15 (\n                    <jats:italic>Tbx15<\/jats:italic>\n                    ). Comparing DCM transcriptional profiles with those in hypertrophic cardiomyopathy (HCM) revealed similar and distinct molecular mechanisms. Our data suggest that cardiomyocyte-specific cytokine expression, early fibroblast activation, and the shift in metabolic gene expression are hallmarks of cardiomyopathy progression. Notably, key components of these profibrotic and metabolic networks were disease specific and distinguish DCM from HCM.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.86898","type":"journal-article","created":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T11:07:07Z","timestamp":1462360027000},"source":"Crossref","is-referenced-by-count":98,"title":["Molecular profiling of dilated cardiomyopathy that progresses to heart failure"],"prefix":"10.1172","volume":"1","author":[{"given":"Michael A.","family":"Burke","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Wakimoto","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Cardiology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Gorham","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Conner","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danos C.","family":"Christodoulou","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, Massachusetts, 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