Genetic deletion of calcium/calmodulin-dependent protein kinase type II delta does not mitigate adverse myocardial remodeling in volume-overloaded hearts

2019 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Genetic deletion of calcium/calmodulin-dependent protein kinase type II delta does not mitigate adverse myocardial remodeling in volume-overloaded hearts​
Mohamed, B. A. ; Elkenani, M.; Jakubiczka-Smorag, J. ; Buchholz, E.; Koszewa, S.; Lbik, D. & Schnelle, M.  et al.​ (2019) 
Scientific Reports9(1) art. 9889​.​ DOI: https://doi.org/10.1038/s41598-019-46332-3 

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Authors
Mohamed, Belal A. ; Elkenani, Manar; Jakubiczka-Smorag, Joanna ; Buchholz, Eric; Koszewa, Sabrina; Lbik, Dawid; Schnelle, Moritz ; Hasenfuss, Gerd ; Toischer, Karl 
Abstract
Calcium/calmodulin-dependent protein kinase type II delta (CaMKIIδ), the predominant CaMKII isoform expressed in the heart, has been implicated in the progression of myocardial infarction- and pressure overload-induced pathological remodeling. However, the role of CaMKIIδ in volume overload (VO) has not been explored. We have previously reported an activation of CaMKII during transition to HF in long-term VO. Here, we address whether CaMKIIδ is critically involved in the mortality, myocardial remodeling, and heart failure (HF) progression in response to VO. CaMKIIδ knockout (δ-KO) and wild-type (WT) littermates were exposed to aortocaval shunt-induced VO, and the progression of adverse myocardial remodeling was assessed by serial echocardiography, histological and molecular analyses. The mortality rates during 10 weeks of VO were similar in δ-KO and WT mice. Both genotypes displayed comparable eccentric myocardial hypertrophy, altered left ventricle geometry, perturbed systolic and diastolic functions after shunt. Additionally, cardiomyocytes hypertrophy, augmented myocyte apoptosis, and up-regulation of hypertrophic genes were also not significantly different in δ-KO versus WT hearts after shunt. Therefore, CaMKIIδ signaling seems to be dispensable for the progression of VO-induced maladaptive cardiac remodeling. Accordingly, we hypothesize that CaMKIIδ-inhibition as a therapeutic approach might not be helpful in the context of VO-triggered HF.
Issue Date
2019
Journal
Scientific Reports 
Project
SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz 
SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur 
SFB 1002 | D04: Bedeutung der Methylierung von RNA (m6A) und des Histons H3 (H3K4) in der Herzinsuffizienz 
SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle 
Working Group
RG Hasenfuß (Transition zur Herzinsuffizienz) 
RG Toischer (Kardiales Remodeling) 
ISSN
2045-2322
eISSN
2045-2322
Language
English

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