Altered cellular protein quality control system modulates cardiomyocyte function in volume overload-induced hypertrophy

  • Volume-induced hypertrophy is one of the risk factors for cardiac morbidity and mortality. In addition, mechanical and metabolic dysfunction, aging, and cellular redox balance are also contributing factors to the disease progression. In this study, we used volume overload (VO), which was induced by an aortocaval fistula in 2-month-old male Wistar rats, and sham-operated animals served as control. Functional parameters were measured by transthoracic echocardiography at termination 4- or 8-months after VO. The animals showed hypertrophic remodeling that was accompanied by mechanical dysfunction and increased cardiomyocyte stiffness. These alterations were reversible upon treatment with glutathione. Cardiomyocyte dysfunction was associated with elevated oxidative stress markers with unchanged inflammatory signaling pathways. In addition, we observed altered phosphorylation status of small heat shock proteins 27 and 70 and diminished protease expression caspases 3 compared to the matched control group, indicating an impaired protein quality control system. Such alterations might be attributed to the increased oxidative stress as anticipated from the enhanced titin oxidation, ubiquitination, and the elevation in oxidative stress markers. Our study showed an early pathological response to VO, which manifests in cardiomyocyte mechanical dysfunction and dysregulated signaling pathways associated with enhanced oxidative stress and an impaired protein quality control system.

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Author:Kamilla GömöriORCiDGND, Melissa HerwigORCiDGND, Roua HassounGND, Heidi BuddeGND, Nusratul MostafiGND, Simin DelalatGND, Suvasini ModiGND, Merima BegovicGND, Tamara SzabadosORCiDGND, Judit PipisGND, Nikolett Farkas-MorvayGND, István LepránGND, Árpád KovácsGND, Andreas MüggeORCiDGND, Péter FerdinandyGND, Anikó GörbeGND, Péter BencsikORCiDGND, Nazha HamdaniORCiDGND
URN:urn:nbn:de:hbz:294-103539
DOI:https://doi.org/10.3390/antiox11112210 
Parent Title (English):Antioxidants
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2023/10/17
Date of first Publication:2022/11/08
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
heat shock proteins; hypertrophy; oxidative stress; protein quality control; volume overload
Volume:11
Issue:11, Article 2210
First Page:2210-1
Last Page:2210-16
Note:
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:St. Josef-Hospital Bochum, Medizinische Klinik II, Klinik für Kardiologie
Institut für Physiologie
Medizinische Fakultät, Interdisziplinäres Institut für Forschung und Lehre (IFL)
Medizinische Fakultät, Abteilung für Zelluläre und Translationale Physiologie
Dewey Decimal Classification:Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit
open_access (DINI-Set):open_access
faculties:Medizinische Fakultät
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International