Unknown,Transcriptomics,Genomics,Proteomics

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CaM Kinase II mediates maladaptive post-infarct remodeling but not acute myocardial ischemia/reperfusion injury

ABSTRACT: Calcium/calmodulin-dependent protein kinase II (CaMKII) was suggested to mediate ischemic myocardial injury and adverse cardiac remodeling. However, the specific functions of the CaMKII isoforms and splice variants in ischemia/reperfusion (I/R) injury have not been investigated yet. Thus, we studied the roles of the CaMKII isoforms and splice variants in I/R by the use of various CaMKII mutant mice. CaMKIIÎ´C was up-regulated already one day after I/R injury but surprisingly, acute I/R injury was neither affected in CaMKIIÎ´-deficient mice, CaMKIIÎ´-deficient mice in which the splice variants CaMKIIÎ´B and C were re-expressed nor in conditional CaMKIIÎ´/Î³ double-knockout mice (DKO). In contrast, 5 weeks after I/R, DKO mice were protected against extensive scar formation and cardiac dysfunction. Leukocyte infiltration was not altered one day but five days after I/R, explaining the late effects of CaMKII deletion on post-I/R remodeling. Other than reported before, we demonstrate that CaMKII is not critically involved in the immediate mechanisms that regulate acute I/R injury but in the process of post-infarct remodeling. We analysed 6 groups in total: 3 groups from wild-type control animals and 3 groups from CaMKII delta/gamma double-KO mice. Sham operated animals served as controls in both wild-type and KO animal groups. 2 different time points in ischia/reperfusion operated animals were investigated: 1 day and 5 days post-surgery.

ORGANISM(S): Mus musculus

SUBMITTER: Carsten Sticht

PROVIDER: E-GEOD-58486 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

CaM Kinase II mediates maladaptive post-infarct remodeling and pro-inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury.

Weinreuter Martin M Kreusser Michael M MM Beckendorf Jan J Schreiter Friederike C FC Leuschner Florian F Lehmann Lorenz H LH Hofmann Kai P KP Rostosky Julia S JS Diemert Nathalie N Xu Chang C Volz Hans Christian HC Jungmann Andreas A Nickel Alexander A Sticht Carsten C Gretz Norbert N Maack Christoph C Schneider Michael D MD Gröne Hermann-Josef HJ Müller Oliver J OJ Katus Hugo A HA Backs Johannes J

EMBO molecular medicine 20141001 10

CaMKII was suggested to mediate ischemic myocardial injury and adverse cardiac remodeling. Here, we investigated the roles of different CaMKII isoforms and splice variants in ischemia/reperfusion (I/R) injury by the use of new genetic CaMKII mouse models. Although CaMKIIδC was upregulated 1 day after I/R injury, cardiac damage 1 day after I/R was neither affected in CaMKIIδ-deficient mice, CaMKIIδ-deficient mice in which the splice variants CaMKIIδB and C were re-expressed, nor in cardiomyocyte- ...[more]

PMID: 25193973

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Dataset Information

CaM Kinase II mediates maladaptive post-infarct remodeling but not acute myocardial ischemia/reperfusion injury

Publications

CaM Kinase II mediates maladaptive post-infarct remodeling and pro-inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury.

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