{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:47:19Z","timestamp":1790207239998,"version":"4.1.0"},"reference-count":84,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,2,25]]},"abstract":"<jats:p>\n                    <jats:italic>FLNC<\/jats:italic>\n                    truncating mutations (\n                    <jats:italic>FLNCtv<\/jats:italic>\n                    ) are prevalent causes of inherited dilated cardiomyopathy (DCM), with a high risk of developing arrhythmogenic cardiomyopathy. We investigated the molecular mechanisms of mutant FLNC in the pathogenesis of arrhythmogenic DCM (a-DCM) using patient-specific induced pluripotent stem cell\u2013derived cardiomyocytes (iPSC-CMs). We demonstrated that iPSC-CMs from two patients with different\n                    <jats:italic>FLNCtv<\/jats:italic>\n                    mutations displayed arrhythmias and impaired contraction. FLNC ablation induced a similar phenotype, suggesting that\n                    <jats:italic>FLNCtv<\/jats:italic>\n                    are loss-of-function mutations. Coimmunoprecipitation and proteomic analysis identified \u03b2-catenin (CTNNB1) as a downstream target. FLNC deficiency induced nuclear translocation of CTNNB1 and subsequently activated the platelet-derived growth factor receptor alpha (PDGFRA) pathway, which were also observed in human hearts with a-DCM and\n                    <jats:italic>FLNCtv<\/jats:italic>\n                    . Treatment with the PDGFRA inhibitor, crenolanib, improved contractile function of patient iPSC-CMs. Collectively, our findings suggest that PDGFRA signaling is implicated in the pathogenesis, and inhibition of this pathway is a potential therapeutic strategy in FLNC-related cardiomyopathies.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.abk0052","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T13:59:33Z","timestamp":1645624773000},"source":"Crossref","is-referenced-by-count":25,"title":["Activation of PDGFRA signaling contributes to filamin C\u2013related arrhythmogenic cardiomyopathy"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9519-9416","authenticated-orcid":true,"given":"Suet Nee","family":"Chen","sequence":"first","affiliation":[{"name":"University of Colorado Cardiovascular Institute, University of Colorado Anschutz Medical Aurora, CO, 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