Age‑related changes in mineralocorticoid receptors in rat hearts

Hu,Danli; Dong,Ruolan; Zhang,Yanjun; Yang,Yan; Chen,Zhihui; Tang,Ying; Fu,Menglu; Xu,Xizhen; Tu,Ling

doi:10.3892/mmr.2020.11260

Age‑related changes in mineralocorticoid receptors in rat hearts

Authors:
- Danli Hu
- Ruolan Dong
- Yanjun Zhang
- Yan Yang
- Zhihui Chen
- Ying Tang
- Menglu Fu
- Xizhen Xu
- Ling Tu
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Affiliations: National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, P.R. China, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Internal Medicine, Division of Cardiology, General Hospital of Puyang Oil Field, Puyang, Henan 457001, P.R. China, Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Internal Medicine, Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: June 19, 2020 https://doi.org/10.3892/mmr.2020.11260
Pages: 1859-1867
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Age-related alterations in the renin-angiotensin-aldosterone system (RAAS) have been reported in the cardiovascular system; however, the detailed mechanism of the RAAS component mineralocorticoid receptors (MR) has not been elucidated. The present study aimed to investigate the associations between MR and cardiac aging in rats, as well as the regulatory effects of oxidative stress and mitochondrial abnormalities in the aging process. MR expression in the hearts of male Sprague‑Dawley rats aged 3 months (young rats) and 24 months (old rats) was evaluated in vivo. In addition, in vitro, H9C2 cells were treated with a specific MR antagonist, eplerenone, in order to investigate the molecular mechanism underlying the inhibition of myocyte aging process. The results demonstrated that MR expression was significantly higher in 24‑month‑old rat hearts compared with in 3‑month‑old rat hearts. These changes were accompanied by increased p53 expression, decreased peroxisome proliferator‑activated receptor γ coactivator‑1α expression, decreased mitochondrial renewal as assessed by electron microscopy, increased oxidative stress and decreased superoxide dismutase. In vitro, selective antagonism of MR partially blocked H2O2‑induced myocardial aging as assessed by p16, p21 and p53 expression levels and excessive reactive oxygen species (ROS) accumulation. These results indicated that increased MR expression may drive age‑related cardiac dysfunction via mitochondrial damage, increased ROS accumulation and an imbalanced redox state.

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