Calcium/calmodulin-dependent protein kinase II couples wnt signaling with histone deacetylase 4 and mediates dishevelled-induced cardiomyopathy

• Verfasst von: Zhang, Min [VerfasserIn]
• Verfasst von: Riffel, Johannes [VerfasserIn]
• Verfasst von: Kreußer, Michael [VerfasserIn]
• Verfasst von: Katus, Hugo [VerfasserIn]
• Verfasst von: Backs, Johannes [VerfasserIn]
• Verfasst von: Hardt, Stefan [VerfasserIn]
• Titel: Calcium/calmodulin-dependent protein kinase II couples wnt signaling with histone deacetylase 4 and mediates dishevelled-induced cardiomyopathy
• Verf.angabe: Zhang Min, Hagenmueller Marco, Riffel Johannes H., Kreusser Michael M., Bernhold Elmar, Fan Jingjing, Katus Hugo A., Backs Johannes, and Hardt Stefan E.
• Jahr: 2015
• Umfang: 10 S.
• Fussnoten: Gesehen am 28.07.2020 ; Originally published 8 Dec 2014
• Titel Quelle: Enthalten in: Hypertension
• Ort Quelle: Baltimore, Md. : Williams & Wilkins, 1979
• Jahr Quelle: 2015
• Band/Heft Quelle: 65(2015), 2, Seite 335-344
• ISSN Quelle: 1524-4563
• DOI: doi:10.1161/HYPERTENSIONAHA.114.04467
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1725687992

Abstract

Activation of Wnt signaling results in maladaptive cardiac remodeling and cardiomyopathy. Recently, calcium/calmodulin-dependent protein kinase II (CaMKII) was reported to be a pivotal participant in myocardial remodeling. Because CaMKII was suggested as a downstream target of noncanonical Wnt signaling, we aimed to elucidate the role of CaMKII in dishevelled-1-induced cardiomyopathy and the mechanisms underlying its function. Dishevelled-1-induced cardiomyopathy was reversed by deletion of neither CaMKIIδ nor CaMKIIγ. Therefore, dishevelled-1-transgenic mice were crossed with CaMKIIδγ double-knockout mice. These mice displayed a normal cardiac phenotype without cardiac hypertrophy, fibrosis, apoptosis, or left ventricular dysfunction. Further mechanistic analyses unveiled that CaMKIIδγ couples noncanonical Wnt signaling to histone deacetylase 4 and myosin enhancer factor 2. Therefore, our findings indicate that the axis, consisting of dishevelled-1, CaMKII, histone deacetylase 4, and myosin enhancer factor 2, is an attractive therapeutic target for prevention of cardiac remodeling and its progression to left ventricular dysfunction.