{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:20:07Z","timestamp":1788315607694,"version":"build-2803163510"},"reference-count":90,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Variants (pathogenic) of the LMNA gene are a common cause of familial dilated cardiomyopathy (DCM), which is characterised by early-onset atrioventricular (AV) block, atrial fibrillation and ventricular tachyarrhythmias (VTs), and progressive heart failure. The unstable internal nuclear lamina observed in LMNA-related DCM is a consequence of the disassembly of lamins A and C. This suggests that LMNA variants produce truncated or alternative forms of protein that alter the nuclear structure and the signalling pathway related to cardiac muscle diseases. To date, the pathogenic mechanisms and phenotypes of LMNA-related DCM have been studied using different platforms, such as patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) and transgenic mice. In this review, point variants in the LMNA gene that cause autosomal dominantly inherited forms of LMNA-related DCM are summarised. In addition, potential therapeutic targets based on preclinical studies of LMNA variants using transgenic mice and human iPSC-CMs are discussed. They include mitochondria deficiency, variants in nuclear deformation, chromatin remodelling, altered platelet-derived growth factor and ERK1\/2-related pathways, and abnormal calcium handling.<\/jats:p>","DOI":"10.3390\/ph17081030","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T13:57:28Z","timestamp":1722866248000},"page":"1030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Pathogenic Mechanisms of and Novel Therapies for Lamin A\/C-Related Dilated Cardiomyopathy Based on Patient-Specific Pluripotent Stem Cell Platforms and Animal Models"],"prefix":"10.3390","volume":"17","author":[{"given":"Xin-Yi","family":"Wu","sequence":"first","affiliation":[{"name":"Cardiology Division, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee-Ki","family":"Lee","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee-Man","family":"Lau","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5599-5090","authenticated-orcid":false,"given":"Ka-Wing","family":"Au","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4934-1562","authenticated-orcid":false,"given":"Yiu-Lam","family":"Tse","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwong-Man","family":"Ng","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Centre for Stem Cell Translational Biology, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Ka","family":"Wong","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Fat","family":"Tse","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Centre for Stem Cell Translational Biology, Hong Kong SAR, China"},{"name":"Cardiac and Vascular Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China"},{"name":"Hong Kong-Guangdong Stem Cell and Regenerative Medicine Research Centre, The University of Hong Kong and Guangzhou Institutes of Biomedicine and Health, Hong Kong SAR, China"},{"name":"Advanced Biomedical Instrumentation Centre, Hong Kong SAR, China"},{"name":"Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/eurheartj\/ehx596","article-title":"Lamin A\/C cardiomyopathy: Young onset, high penetrance, and frequent need for heart transplantation","volume":"39","author":"Hasselberg","year":"2018","journal-title":"Eur. 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