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Cholesterol-diet leads to attenuation of ischemic preconditioning-induced cardiac protection: the role of connexin43.
MedLine Citation:
PMID:  21398600     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cardioprotection by ischemic preconditioning (IP) was abolished in connexin 43 (Cx43)-deficient mice due to loss of Cx43 located in mitochondria rather than at the sarcolemma. IP is lost in hyperlipidemic rat hearts as well. Since changes in mitochondrial Cx43 in hyperlipidemia have not yet been analyzed, we determined total and mitochondrial Cx43 levels in male Wistar rats fed a laboratory chow enriched with 2% cholesterol or normal chow for 12 weeks. Hearts were isolated and perfused according to Langendorff. After 10 min perfusion myocardial tissue cholesterol, superoxide and nitrotyrosine contents were measured and Cx43 content in whole heart homogenate and a mitochondrial fraction determined. In the cholesterol-fed group, tissue cholesterol and superoxide formation was increased (p<0.05), while total Cx43 content remained unchanged. Mitochondrial total and dephosphorylated Cx43 content decreased. Hearts were subjected to an IP protocol (3X5 min ischemia/reperfusion) or time-matched aerobic perfusion followed by 30 min global ischemia and 5 min reperfusion. IP reduced infarct size in normal but not in cholesterol-fed rats. At 5 min reperfusion following 30 min global ischemia the total and dephosphorylated mitochondrial Cx43 content was increased which was abolished by IP in both normal and high-cholesterol diet. In conclusion, loss of cardioprotection by IP in hyperlipidemia is associated with a redistribution of both sarcolemmal and mitochondrial Cx43.
Authors:
Aniko Görbe; Zoltán V Varga; Krisztina Kupai; Peter Bencsik; Gabriella F Kocsis; Tamas Csont; Kerstin Boengler; Rainer Schulz; Peter Ferdinandy
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-11
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1University of Szeged.
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