{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:09:37Z","timestamp":1792786177693,"version":"4.5.0"},"posted":{"date-parts":[[2025,6,6]]},"group-title":"Cell Biology","reference-count":72,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH\/NHLBI","award":["R00HL118163"],"award-info":[{"award-number":["R00HL118163"]}]},{"name":"NIH\/NHLBI","award":["R01HL150019"],"award-info":[{"award-number":["R01HL150019"]}]},{"award":["S10 OD010408"],"award-info":[{"award-number":["S10 OD010408"]}],"id":[{"id":"https:\/\/ror.org\/00fj8a872","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Genetic cardiomyopathies arising from mutations in the\n                  <jats:italic>LMNA<\/jats:italic>\n                  gene, encoding nuclear intermediate filaments lamin A\/C, display variable age of onset, severity, and fibrosis development. This variability suggests a fundamental element in disease pathogenesis that has yet to be elucidated. Given the central role cardiac fibroblasts play in fibrosis, we explored the relevance of lamin A\/C in cardiac fibroblast function, as very little is known in this regard. Using primary cardiac fibroblasts and\n                  <jats:italic>in vivo<\/jats:italic>\n                  mouse models, we show that\n                  <jats:italic>Lmna<\/jats:italic>\n                  mutations impact various aspects of cardiac fibroblast function in response to myocyte damage. We show that both lamin A\/C depletion and point-mutant variant expression impair cardiac fibroblast proliferation and contraction whereas other functions such as cell migration appears to be mutation dependent.\n                  <jats:italic>In vivo<\/jats:italic>\n                  depletion of lamin A\/C simultaneously in cardiomyocytes and cardiac fibroblasts significantly delayed disease progression, improved cardiac function, and prolonged survival, indicating that lamin A\/C mediate an opposing balance between cardiomyocytes and cardiac fibroblasts in driving disease pathogenesis. Our results elucidate previously unexplored roles of lamin A\/C in cardiac fibroblasts and suggest that interactions between cardiac fibroblasts and cardiomyocytes are important determinants of the rate of progression and the severity of\n                  <jats:italic>LMNA<\/jats:italic>\n                  cardiomyopathy.\n                <\/jats:p>","DOI":"10.1101\/2025.06.05.657412","type":"posted-content","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T07:50:10Z","timestamp":1749196210000},"source":"Crossref","is-referenced-by-count":2,"title":["Cardiac fibroblasts counterbalance cardiomyocytes in\n                  <i>LMNA<\/i>\n                  cardiomyopathy pathogenesis"],"prefix":"10.64898","author":[{"given":"Kunal","family":"Sikder","sequence":"first","affiliation":[{"name":"Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia 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