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Developing effective clinical cardioprotection strategies would make a significant impact in improving both quality of life and longevity in the worldwide population. Both ex vivo and in vivo animal models of cardiac ischemia\/reperfusion (I\/R) injury are robustly used in research. Connexin43 (Cx43), the predominant gap junction channel-forming protein in cardiomyocytes, has emerged as a cardioprotective target. Cx43 posttranslational modifications as well as cellular distribution are altered during cardiac reperfusion injury, inducing phosphorylation states and localization detrimental to maintaining intercellular communication and cardiac conduction. Pre- (before ischemia) and post- (after ischemia but before reperfusion) conditioning can abrogate this injury process, preserving Cx43 and reducing cell death. Pre-\/post-conditioning has been shown to largely rely on the presence of Cx43, including mitochondrial Cx43, which is implicated to play a major role in pre-conditioning. Posttranslational modifications of Cx43 after injury alter the protein interactome, inducing negative protein cascades and altering protein trafficking, which then causes further damage post-I\/R injury. Recently, several peptides based on the Cx43 sequence have been found to successfully diminish cardiac injury in pre-clinical studies.<\/jats:p>","DOI":"10.3390\/biom10091225","type":"journal-article","created":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T21:28:06Z","timestamp":1598218086000},"page":"1225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection"],"prefix":"10.3390","volume":"10","author":[{"given":"Olga M.","family":"Rusiecka","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva, Switzerland"}]},{"given":"Jade","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1538-3553","authenticated-orcid":false,"given":"Sandrine","family":"Morel","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1931-9076","authenticated-orcid":false,"given":"Daniela","family":"Batista-Almeida","sequence":"additional","affiliation":[{"name":"Univ Coimbra, Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, 3000-548 Coimbra, Portugal"},{"name":"Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Centre of Coimbra (CACC), 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4340-0210","authenticated-orcid":false,"given":"Raf","family":"Van Campenhout","sequence":"additional","affiliation":[{"name":"Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}]},{"given":"Mathieu","family":"Vinken","sequence":"additional","affiliation":[{"name":"Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5786-8447","authenticated-orcid":false,"given":"Henrique","family":"Girao","sequence":"additional","affiliation":[{"name":"Univ Coimbra, Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, 3000-548 Coimbra, Portugal"},{"name":"Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Centre of Coimbra (CACC), 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0015-0044","authenticated-orcid":false,"given":"Brenda R.","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva, Switzerland"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/CIRCRESAHA.117.308903","article-title":"Reducing the global burden of cardiovascular disease, part 1: The epidemiology and risk factors","volume":"121","author":"Joseph","year":"2017","journal-title":"Circ. 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