Open AccessCa M Kinase II mediates maladaptive post‐infarct remodeling and pro‐inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury
Author(s) -
Weinreuter Martin,
Kreusser Michael M,
Beckendorf Jan,
Schreiter Friederike C,
Leuschner Florian,
Lehmann Lorenz H,
Hofmann Kai P,
Rostosky Julia S,
Diemert Nathalie,
Xu Chang,
Volz Hans Christian,
Jungmann Andreas,
Nickel Alexander,
Sticht Carsten,
Gretz Norbert,
Maack Christoph,
Schneider Michael D,
Gröne HermannJosef,
Müller Oliver J,
Katus Hugo A,
Backs Johannes
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201403848
Subject(s) - chemokine , inflammation , downregulation and upregulation , ischemia , gene isoform , knockout mouse , reperfusion injury , chemotaxis , chemistry , microbiology and biotechnology , medicine , receptor , pharmacology , immunology , biology , biochemistry , gene
Ca MKII was suggested to mediate ischemic myocardial injury and adverse cardiac remodeling. Here, we investigated the roles of different Ca MKII isoforms and splice variants in ischemia/reperfusion (I/R) injury by the use of new genetic Ca MKII mouse models. Although Ca MKII δC was upregulated 1 day after I/R injury, cardiac damage 1 day after I/R was neither affected in Ca MKII δ‐deficient mice, Ca MKII δ‐deficient mice in which the splice variants Ca MKII δB and C were re‐expressed, nor in cardiomyocyte‐specific Ca MKII δ/γ double knockout mice ( DKO ). In contrast, 5 weeks after I/R, DKO mice were protected against extensive scar formation and cardiac dysfunction, which was associated with reduced leukocyte infiltration and attenuated expression of members of the chemokine (C‐C motif) ligand family, in particular CCL 3 (macrophage inflammatory protein‐1α, MIP ‐1α). Intriguingly, Ca MKII was sufficient and required to induce CCL 3 expression in isolated cardiomyocytes, indicating a cardiomyocyte autonomous effect. We propose that Ca MKII ‐dependent chemoattractant signaling explains the effects on post‐I/R remodeling. Taken together, we demonstrate that Ca MKII is not critically involved in acute I/R‐induced damage but in the process of post‐infarct remodeling and inflammatory processes.