Details

Autor(en) / Beteiligte

• 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, Hermann‐Josef
• Müller, Oliver J
• Katus, Hugo A
• Backs, Johannes

Titel

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

Ist Teil von

• EMBO molecular medicine, 2014-10, Vol.6 (10), p.1231-1245

Ort / Verlag

England: John Wiley & Sons, Inc

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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‐specific CaMKIIδ/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 CCL3 (macrophage inflammatory protein‐1α, MIP‐1α). Intriguingly, CaMKII was sufficient and required to induce CCL3 expression in isolated cardiomyocytes, indicating a cardiomyocyte autonomous effect. We propose that CaMKII‐dependent chemoattractant signaling explains the effects on post‐I/R remodeling. Taken together, we demonstrate that CaMKII is not critically involved in acute I/R‐induced damage but in the process of post‐infarct remodeling and inflammatory processes. Synopsis CaMKII is critically involved in post‐infarct remodelling via the activation of inflammatory pathways. At variance with previous reports, however, CaMKII does not appear to be relevant in acute damage after ischemia/reperfusion (I/R) injury. Acute myocardial I/R‐induced damage is not mediated by CaMKII whereas post‐I/R remodelling and inflammatory processes are. Leukocyte infiltration and expression of members of the chemokine (C‐C motif) ligand family, in particular CCL3 (macrophage inflammatory protein‐1a, MIP‐1a), are reduced in mice lacking the two cardiac CaMKII isoforms delta and gamma upon I/R injury. CaMKII is sufficient and required for CCL3 expression in cardiomyocytes. CaMKII is critically involved in post‐infarct remodelling via the activation of inflammatory pathways. At variance with previous reports, however, CaMKII does not appear to be relevant in acute damage after ischemia/reperfusion injury.