{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T18:18:54Z","timestamp":1762453134413,"version":"build-2065373602"},"reference-count":83,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health, Ricerca Corrente to Centro Cardiologico Monzino IRCCS","doi-asserted-by":"publisher","award":["2775033"],"award-info":[{"award-number":["2775033"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020407","name":"ERA-CVD","doi-asserted-by":"publisher","award":["ACM-HF JTC2016-40-021"],"award-info":[{"award-number":["ACM-HF JTC2016-40-021"]}],"id":[{"id":"10.13039\/501100020407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Arrhythmogenic cardiomyopathy (ACM) is a cardiac disorder manifesting through electrical and contractile dysfunction of the ventricles, characterized by fibro-fatty substitution of the myocardium. Cardiac mesenchymal stromal cells (CMSCs) are key contributors to this remodeling. In clinical management, several pharmacological approaches address ACM arrhythmias and heart failure, but, to date, none specifically target fibro-adipose replacement. Despite genetic origin, several studies have reported that non-genetic aspects influence ACM phenotype, including epigenetic factors. Little is known about their mechanisms in ACM and their potential therapeutic applications. In this work, we aimed to test whether, by perturbing the epigenetic landscape of ACM CMSCs, we could influence their propensity to fibro-fatty differentiation. We conducted a hypothesis-free screening of 157 epigenetic drugs on CMSCs, isolated from ACM patients. Through fluorescence assays, we evaluated lipid droplet accumulation, collagen deposition, and cell viability. Of the 157 drugs screened, five (splitomicin, suberohydroxamic acid, CPTH6, BVT-948, and PBIT) attenuated adipogenic differentiation of ACM CMSCs, with BVT-948 and CPTH6 also reducing collagen production. Overall, this study identified specific epigenetic drugs that were effective in reducing the fibro-fatty phenotype of ACM stromal cells, thus offering potential for adjunctive therapies in the clinical management of ACM patients.<\/jats:p>","DOI":"10.3390\/biom15111565","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:51:43Z","timestamp":1762451503000},"page":"1565","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic Drugs Splitomicin, Suberohydroxamic Acid, CPTH6, BVT-948, and PBIT Moderate Fibro-Fatty Development in Arrhythmogenic Cardiomyopathy"],"prefix":"10.3390","volume":"15","author":[{"given":"Melania","family":"Lippi","sequence":"first","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"},{"name":"Department of Medicine and Surgery, Universit\u00e0 degli Studi di Milano Bicocca, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Moimas","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB), 34139 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Braga","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB), 34139 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohan","family":"Santin","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9561-9436","authenticated-orcid":false,"given":"Arianna","family":"Galotta","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Giacca","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB), 34139 Trieste, Italy"},{"name":"British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulio","family":"Pompilio","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Sommariva","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","unstructured":"(2025, May 24). 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