Aldosterone Excess Induced Mitochondria Decrease and Dysfunction via Mineralocorticoid Receptor and Oxidative Stress In Vitro and In Vivo
Cheng-Hsuan Tsai,
Chien-Ting Pan,
Yi-Yao Chang,
Shih-Yuan Peng,
Po-Chin Lee,
Che-Wei Liao,
Chia-Tung Shun,
Po-Ting Li,
Vin-Cent Wu,
Chia-Hung Chou,
I-Jung Tsai,
Chi-Sheng Hung,
Yen-Hung Lin
Affiliations
Cheng-Hsuan Tsai
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan
Chien-Ting Pan
Department of Internal Medicine, Division of Cardiology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan
Yi-Yao Chang
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan
Shih-Yuan Peng
Department of Internal Medicine, Division of Cardiology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan
Po-Chin Lee
Department of Medical Imaging, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan
Che-Wei Liao
Department of Internal Medicine, Division of Cardiology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan
Chia-Tung Shun
Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei 100, Taiwan
Po-Ting Li
Department of Internal Medicine, Division of Cardiology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan
Vin-Cent Wu
Division of Nephrology, Department of Internal Medicine, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan
Chia-Hung Chou
Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan
I-Jung Tsai
Division of Nephrology, Department of Pediatrics, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan
Chi-Sheng Hung
Department of Internal Medicine, Division of Cardiology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan
Yen-Hung Lin
Department of Internal Medicine, Division of Cardiology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan
Aldosterone excess plays a major role in the progression of cardiac dysfunction and remodeling in clinical diseases such as primary aldosteronism and heart failure. However, the effect of aldosterone excess on cardiac mitochondria is unclear. In this study, we investigated the effect of aldosterone excess on cardiac mitochondrial dysfunction and its mechanisms in vitro and in vivo. We used H9c2 cardiomyocytes to investigate the effect and mechanism of aldosterone excess on cardiac mitochondria, and further investigated them in an aldosterone-infused ICR mice model. The results of the cell study showed that aldosterone excess decreased mitochondrial DNA, COX IV and SOD2 protein expressions, and mitochondria ATP production. These effects were abolished or attenuated by treatment with a mineralocorticoid receptor (MR) antagonist and antioxidant. With regard to the signal transduction pathway, aldosterone suppressed cardiac mitochondria through an MR/MAPK/p38/reactive oxygen species pathway. In the mouse model, aldosterone infusion decreased the amount of cardiac mitochondrial DNA and COX IV protein, and the effects were also attenuated by treatment with an MR antagonist and antioxidant. In conclusion, aldosterone excess induced a decrease in mitochondria and mitochondrial dysfunction via MRs and oxidative stress in vitro and in vivo.
