Research Paper Volume 12, Issue 23 pp 24117—24133
Dilated cardiomyopathy impairs mitochondrial biogenesis and promotes inflammation in an age- and sex-dependent manner
- 1 Clinic for Geriatrics, Charité University Hospital, Berlin, Germany
- 2 DZHK (German Centre for Cardiovascular Research), Berlin Partner Site, Berlin, Germany
- 3 Climate and Health Program (CLIMA), Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain
- 4 Charité, Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt, Universität zu Berlin, Berlin Institute of Health, iPATH Berlin-Immunopathology for Experimental Models, Berlin, Germany
- 5 Erich and Hanna Klessmann Institute, Heart and Diabetes Centre NRW, University Hospital of the Ruhr-University Bochum, Bad Oeynhausen, Germany
- 6 Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary
- 7 Institute for Gender in Medicine, Center for Cardiovascular Research, Charité University Hospital, Berlin, Germany
- 8 Department of Cardiology, University Hospital Zürich, University of Zürich, Zürich, Switzerland
Received: July 28, 2020 Accepted: September 29, 2020 Published: December 2, 2020
https://doi.org/10.18632/aging.202283How to Cite
Copyright: © 2020 Barcena et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Dilated cardiomyopathy (DCM) belongs to the myocardial diseases associated with a severe impairment of cardiac function, but the question of how sex and age affect this pathology has not been fully explored. Impaired energy homeostasis, mitochondrial dysfunction, and systemic inflammation are well-described phenomena associated with aging. In this study, we investigated if DCM affects these phenomena in a sex- and age-related manner.
We analyzed the expression of mitochondrial and antioxidant proteins and the inflammatory state in DCM heart tissue from younger and older women and men.
A significant downregulation of Sirt1 expression was detected in older DCM patients. Sex-related differences were observed in the phosphorylation of AMPK that only appeared in older males with DCM, possibly due to an alternative Sirt1 regulation mechanism. Furthermore, reduced expression of several mitochondrial proteins (TOM40, TIM23, Sirt3, and SOD2) and genes (cox1, nd4) was only detected in old DCM patients, suggesting that age has a greater effect than DCM on these alterations. Finally, an increased expression of inflammatory markers in older, failing hearts, with a stronger pro-inflammatory response in men, was observed. Together, these findings indicate that age- and sex-related increased inflammation and disturbance of mitochondrial homeostasis occurs in male individuals with DCM.