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Current therapies are aimed to prevent the worsening of disease phenotypes and sudden cardiac death (SCD). Despite the use of implantable cardioverter defibrillators (ICDs) there is no present therapy that would mitigate the loss in electrical signal and propagation by these fibrofatty barriers. Recent studies have shown the influence of forced vs. voluntary exercise in a variety of healthy and diseased mice; more specifically, that exercised mice show increased Connexin-43 (Cx43) expression levels. Fascinatingly, increased Cx43 expression ameliorated the abnormal electrical signal conduction in the myocardium of diseased mice. These findings point to a major translational pitfall in current therapeutics for ACM patients, who are advised to completely cease exercising and already demonstrate reduced Cx43 levels at the myocyte intercalated disc. Considering cardiac dysfunction in ACM arises from the loss of cardiomyocytes and electrical signal conduction abnormalities, an increase in Cx43 expression\u2014promoted by low to moderate intensity exercise and\/or gene therapy\u2014could very well improve cardiac function in ACM patients.<\/jats:p>","DOI":"10.3390\/ijms23158753","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T22:51:46Z","timestamp":1659912706000},"page":"8753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Arrhythmogenic Cardiomyopathy: Exercise Pitfalls, Role of Connexin-43, and Moving beyond Antiarrhythmics"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9706-9319","authenticated-orcid":false,"given":"Isabella Leite","family":"Coscarella","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6696-8888","authenticated-orcid":false,"given":"Maicon","family":"Landim-Vieira","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Renato","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1675-5945","authenticated-orcid":false,"given":"Stephen P.","family":"Chelko","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32303, USA"},{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e009611","DOI":"10.1161\/JAHA.118.009611","article-title":"Exercise: A Risky Subject in Arrhythmogenic Cardiomyopathy","volume":"7","author":"Cerrone","year":"2018","journal-title":"J. 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