Canonical and non-canonical roles of connexin43 in cardioprotection

Olga M. Rusiecka, Jade Montgomery, Sandrine Morel, Daniela Batista-Almeida, Raf Van Campenhout, Mathieu Vinken, Henrique Girao, Brenda R. Kwak

Research output: Contribution to journalArticle

2 Citations (Scopus)
1 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article number1225
Pages (from-to)1-22
Number of pages22
JournalBiomolecules
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 2020

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