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

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. CaMKIIC was up-regulated already one day after I/R injury but surprisingly, acute I/R injury was neither affected in CaMKII-deficient mice, CaMKII-deficient mice in which the splice variants CaMKIIB and C were re-expressed nor in conditional CaMKII/ 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.

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Weinreuter M, Kreusser MM, Beckendorf J, Schreiter FC, Leuschner F, Lehmann LH, Hofmann KP, Rostosky JS, Diemert N, Xu C, Volz HC, Jungmann A, Nickel A, Sticht C, Gretz N, Maack C, Schneider MD, Gröne HJ, Müller OJ, Katus HA, Backs J