title: Cholesterol diet leads to attenuation of ischemic preconditioning-induced cardiac protection: the role of connexin 43.
abstract: 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 wk. Hearts were isolated and perfused according to Langendorff. After a 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 (3 × 5 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.affiliation: Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Hungary.
authors.forename: Anikó
authors.initials: A
authors.lastname: Görbe
authors.forename: Zoltán V
authors.initials: ZV
authors.lastname: Varga
authors.forename: Krisztina
authors.initials: K
authors.lastname: Kupai
authors.forename: Péter
authors.initials: P
authors.lastname: Bencsik
authors.forename: Gabriella F
authors.initials: GF
authors.lastname: Kocsis
authors.forename: Tamás
authors.initials: T
authors.lastname: Csont
authors.forename: Kerstin
authors.initials: K
authors.lastname: Boengler
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000627:therapeutic use*; D018031:Connexin 43 / Q000378:metabolism*; D006949:Hyperlipidemias / Q000378:metabolism* / Q000503:physiopathology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D023421:Models, Animal; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D002791:Cholesterol, Dietary; D018031:Connexin 43; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; D002784:Cholesterol