title: Loss of ischemic preconditioning's cardioprotection in aged mouse hearts is associated with reduced gap junctional and mitochondrial levels of connexin 43.
abstract: Connexin 43 (Cx43) is localized at left ventricular (LV) gap junctions and in cardiomyocyte mitochondria. A genetically induced reduction of Cx43 as well as blockade of mitochondrial Cx43 import abolishes the infarct size (IS) reduction by ischemic preconditioning (IP). With progressing age, Cx43 content in ventricular and atrial tissue homogenates is reduced. We now investigated whether or not 1) the mitochondrial Cx43 content is reduced in aged mice hearts and 2) IS reduction by IP is lost in aged mice hearts in vivo. Confirming previous results, sarcolemmal Cx43 content was reduced in aged (>13 mo) compared with young (<3 mo) C57Bl/6 mice hearts, whereas the expression levels of protein kinase C epsilon and endothelial nitric oxide synthase remained unchanged. Also in mitochondria isolated from aged mice LV myocardium, Western blot analysis indicated a 40% decrease in Cx43 content compared with mitochondria isolated from young mice hearts. In young mice hearts, IP by one cycle of 10 min ischemia and 10 min reperfusion reduced IS (% of area at risk) following 30 min regional ischemia and 120 min reperfusion from 67.7 +/- 3.3 (n = 17) to 34.2 +/- 6.6 (n = 5, P < 0.05). In contrast, IP's cardioprotection was lost in aged mice hearts, since IS in nonpreconditioned (57.5 +/- 4.0, n = 10) and preconditioned hearts (65.4 +/- 6.3, n = 8, P = not significant) was not different. In conclusion, mitochondrial Cx43 content is decreased in aged mouse hearts. The reduced levels of Cx43 may contribute to the age-related loss of cardioprotection by IP.
authors.affiliation: Institut für Pathophysiologie, Universitätsklinikum Essen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Boengler
authors.forename: Ina
authors.initials: I
authors.lastname: Konietzka
authors.forename: Astrid
authors.initials: A
authors.lastname: Buechert
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Heinen
authors.forename: David
authors.initials: D
authors.lastname: Garcia-Dorado
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D018031:Connexin 43 / Q000378:metabolism*; D005260:Female; D017629:Gap Junctions / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D019157:Ischemic Preconditioning, Myocardial; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology
chemical_list: D018031:Connexin 43