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

Medientyp: E-Artikel
Titel: CaM Kinase II mediates maladaptive post‐infarct remodeling and pro‐inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury
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
Erschienen: Springer Science and Business Media LLC, 2014
Erschienen in: EMBO Molecular Medicine
Sprache: Englisch
DOI: 10.15252/emmm.201403848
ISSN: 1757-4676; 1757-4684
Entstehung:
Anmerkungen:
Beschreibung: <jats:title>Abstract</jats:title><jats:p>Ca<jats:styled-content style="fixed-case">MKII</jats:styled-content> was suggested to mediate ischemic myocardial injury and adverse cardiac remodeling. Here, we investigated the roles of different Ca<jats:styled-content style="fixed-case">MKII</jats:styled-content> isoforms and splice variants in ischemia/reperfusion (I/R) injury by the use of new genetic Ca<jats:styled-content style="fixed-case">MKII</jats:styled-content> mouse models. Although Ca<jats:styled-content style="fixed-case">MKII</jats:styled-content>δC was upregulated 1 day after I/R injury, cardiac damage 1 day after I/R was neither affected in Ca<jats:styled-content style="fixed-case">MKII</jats:styled-content>δ‐deficient mice, Ca<jats:styled-content style="fixed-case">MKII</jats:styled-content>δ‐deficient mice in which the splice variants Ca<jats:styled-content style="fixed-case">MKII</jats:styled-content>δB and C were re‐expressed, nor in cardiomyocyte‐specific Ca<jats:styled-content style="fixed-case">MKII</jats:styled-content>δ/γ double knockout mice (<jats:styled-content style="fixed-case">DKO</jats:styled-content>). In contrast, 5 weeks after I/R, <jats:styled-content style="fixed-case">DKO</jats:styled-content> 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 <jats:styled-content style="fixed-case">CCL</jats:styled-content>3 (macrophage inflammatory protein‐1α, <jats:styled-content style="fixed-case">MIP</jats:styled-content>‐1α). Intriguingly, Ca<jats:styled-content style="fixed-case">MKII</jats:styled-content> was sufficient and required to induce <jats:styled-content style="fixed-case">CCL</jats:styled-content>3 expression in isolated cardiomyocytes, indicating a cardiomyocyte autonomous effect. We propose that Ca<jats:styled-content style="fixed-case">MKII</jats:styled-content>‐dependent chemoattractant signaling explains the effects on post‐I/R remodeling. Taken together, we demonstrate that Ca<jats:styled-content style="fixed-case">MKII</jats:styled-content> is not critically involved in acute I/R‐induced damage but in the process of post‐infarct remodeling and inflammatory processes.</jats:p>
Zugangsstatus: Freier Zugang

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: