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Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection.

  • Rusiecka OM Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva, Switzerland.
  • Montgomery J Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva, Switzerland.
  • Morel S Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva, Switzerland.
  • Batista-Almeida D Univ Coimbra, Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, 3000-548 Coimbra, Portugal.
  • Van Campenhout R Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
  • Vinken M Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
  • Girao H Univ Coimbra, Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, 3000-548 Coimbra, Portugal.
  • Kwak BR Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva, Switzerland.
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  • 2020-08-27
Published in:
  • Biomolecules. - 2020
Cx43
cardioprotection
connexin
gap junction
hemi-channel
ischemia/reperfusion injury
myocardial infarction
English 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.
Language
  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/100570
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