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Single Intravenous Low-Dose Injections of Connexin 43 Mimetic Peptides Protect Ischemic Heart In Vivo Against Myocardial Infarction.
MedLine Citation:
PMID:  22841862     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The opening of unapposed connexin 43 hemichannels (Cx43Hc) under ischemic stress leads to cell death and irreversible tissue injury. Here, we investigate for the first time in vivo the cardioprotective potentials of two unique Cx43 structural-mimetic peptides (Cx43MPs) presumed specific blockers of Cx43Hc, Gap26 and Gap27, when injected intravenously using a rat model of myocardial infarction. Sprague Dawley rats were utilized. Myocardial infarction was induced by occluding the left anterior descendent coronary during 40min followed by 2days of reperfusion. Interestingly, single bolus injections of Gap26 or Gap27 (1μg/Kg) into jugular vein caused infarct size reductions by up to 61% with reference to control rats injected with saline at similar timings. Infarct reductions did not vary significantly whether peptides were administered before or after the onset of ischemia. Although the two peptides allegedly interact with distinct structures of Cx43, co-administration of Gap26/Gap27 in equal doses did not confer additive protection to hearts (maximum infarct reduction by 64%). Using patch clamp technique, we provide unique and direct evidence for the inhibitory effect of Cx43MPs on genuine human Cx43Hc transiently expressed in the ion channel-deficient tsA201 cells. In concordance with the cardioprotective effect observed in vivo, co-application of both peptides did not cause cumulative current inhibition. A safety profile of Cx43MPs was also addressed. Our results reveal great therapeutic potential of Cx43MPs in treatment of myocardial infarction. Their practical way and timing of administration and their apparent safe profile make them promising tools to fight ischemic heart disease.
Authors:
Ghayda Hawat; Pierre Hélie; Ghayath Baroudi
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-26
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  -     ISSN:  1095-8584     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Affiliation:
Centre de recherche, Hôpital du Sacré-Cœur de Montréal, Université de Montréal, Montréal, Québec, Canada; Département de pharmacologie, Faculté de médecine, Université de Montréal, Montréal, Québec, Canada.
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