Hemodynamic stress-induced cardiac remodelling is not modulated by ablation of phosphodiesterase 4D interacting protein
2022-08 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Hemodynamic stress-induced cardiac remodelling is not modulated by ablation of phosphodiesterase 4D interacting protein
Mohamed, B. A. ; Elkenani, M.; Mobarak, S.; Marques Rodrigues, D.; Annamalai, K.; Schnelle, M. & Bader, M. et al. (2022)
Journal of Cellular and Molecular Medicine, 26(16) pp. 4440-4452. DOI: https://doi.org/10.1111/jcmm.17468
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- Authors
- Mohamed, Belal A. ; Elkenani, Manar; Mobarak, Sherok; Marques Rodrigues, Daniel; Annamalai, Karthika; Schnelle, Moritz ; Bader, Michael; Hasenfuss, Gerd ; Toischer, Karl
- Abstract
- Adrenergic stimulation in the heart activates the protein kinase A (PKA), which phosphorylates key proteins involved in intracellular Ca2+ handling. PKA is held in proximity to its substrates by protein scaffolds, the A kinase anchoring proteins (AKAPs). We have previously identified the transcript of phosphodiesterase 4D interacting protein (Pde4dip; also known as myomegalin), one of the sarcomeric AKAPs, as being differentially expressed following hemodynamic overload, a condition inducing hyperadrenergic state in the heart. Here, we addressed whether PDE4DIP is involved in the adverse cardiac remodelling following hemodynamic stress. Homozygous Pde4dip knockout (KO) mice, generated by CRISPR-Cas9 technology, and wild-type (WT) littermates were exposed to aortocaval shunt (shunt) or transthoracic aortic constriction (TAC) to induce hemodynamic volume overload (VO) or pressure overload (PO), respectively. The mortality, cardiac structure, function and pathological cardiac remodelling were followed up after hemodynamic injuries. The PDE4DIP protein level was markedly downregulated in volume-overloaded- but upregulated in pressure-overloaded-WT hearts. Following shunt or TAC, mortality rates were comparably increased in both genotypes. Twelve weeks after shunt or TAC, Pde4dip-KO animals showed a similar degree of cardiac hypertrophy, dilatation and dysfunction as WT mice. Cardiomyocyte hypertrophy, myocardial fibrosis, reactivation of cardiac stress genes and downregulation of ATPase, Ca2+ transporting, cardiac muscle, slow twitch 2 transcript did not differ between WT and Pde4dip-KO hearts following shunt or TAC. In summary, despite a differential expression of PDE4DIP protein in remodelled WT hearts, Pde4dip deficiency does not modulate adverse cardiac remodelling after hemodynamic VO or PO.
- Issue Date
- August-2022
- Journal
- Journal of Cellular and Molecular Medicine
- 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 - Working Group
- RG Hasenfuß (Transition zur Herzinsuffizienz)
RG Toischer (Kardiales Remodeling) - ISSN
- 1582-1838; 1582-4934
- eISSN
- 1582-4934
- Language
- English
- Sponsor
- Open-Access-Publikationsfonds 2022