Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection
Since the mid-20th century, ischemic heart disease has been the world’s leading cause of death. 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 model...
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MDPI AG
2020-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/9/1225 |
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| author | Olga M. Rusiecka Jade Montgomery Sandrine Morel Daniela Batista-Almeida Raf Van Campenhout Mathieu Vinken Henrique Girao Brenda R. Kwak |
| author_facet | Olga M. Rusiecka Jade Montgomery Sandrine Morel Daniela Batista-Almeida Raf Van Campenhout Mathieu Vinken Henrique Girao Brenda R. Kwak |
| author_sort | Olga M. Rusiecka |
| collection | DOAJ |
| description | Since the mid-20th century, ischemic heart disease has been the world’s leading cause of death. 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. |
| first_indexed | 2024-03-10T16:58:10Z |
| format | Article |
| id | doaj.art-9748dcb0f1c04afa9cde478df9da8a97 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T16:58:10Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-9748dcb0f1c04afa9cde478df9da8a972023-11-20T11:03:53ZengMDPI AGBiomolecules2218-273X2020-08-01109122510.3390/biom10091225Canonical and Non-Canonical Roles of Connexin43 in CardioprotectionOlga M. Rusiecka0Jade Montgomery1Sandrine Morel2Daniela Batista-Almeida3Raf Van Campenhout4Mathieu Vinken5Henrique Girao6Brenda R. Kwak7Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva, SwitzerlandDepartment of Pathology and Immunology, University of Geneva, CH-1211 Geneva, SwitzerlandDepartment of Pathology and Immunology, University of Geneva, CH-1211 Geneva, SwitzerlandUniv Coimbra, Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, 3000-548 Coimbra, PortugalDepartment of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, BelgiumDepartment of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, BelgiumUniv Coimbra, Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, 3000-548 Coimbra, PortugalDepartment of Pathology and Immunology, University of Geneva, CH-1211 Geneva, SwitzerlandSince the mid-20th century, ischemic heart disease has been the world’s leading cause of death. 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.https://www.mdpi.com/2218-273X/10/9/1225connexinCx43gap junctionhemi-channelcardioprotectionmyocardial infarction |
| spellingShingle | Olga M. Rusiecka Jade Montgomery Sandrine Morel Daniela Batista-Almeida Raf Van Campenhout Mathieu Vinken Henrique Girao Brenda R. Kwak Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection Biomolecules connexin Cx43 gap junction hemi-channel cardioprotection myocardial infarction |
| title | Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection |
| title_full | Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection |
| title_fullStr | Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection |
| title_full_unstemmed | Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection |
| title_short | Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection |
| title_sort | canonical and non canonical roles of connexin43 in cardioprotection |
| topic | connexin Cx43 gap junction hemi-channel cardioprotection myocardial infarction |
| url | https://www.mdpi.com/2218-273X/10/9/1225 |
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