Aldosterone suppresses cardiac mitochondria.
Autor: | Hung CS (啟盛) 628401; Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (R.O.C.). Electronic address: petrehcs@gmail.com., Chang YY; Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan (R.O.C.). Electronic address: rollerpapa@gmail.com., Tsai CH; Department of Internal Medicine, National Taiwan University Hospital Jinshan Branch, New Taipei City , Taiwan (R.O.C.). Electronic address: cheng.hsuan.richard.tsai@gmail.com., Liao CW; Department of Medicine, National Taiwan, University Cancer Center, Taipei, Taiwan (R.O.C.). Electronic address: yo.ahliao@gmail.com., Peng SY; Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (R.O.C.). Electronic address: sypeng0302.12@gmail.com., Lee BC; Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (R.O.C.). Electronic address: bochinglee@gmail.com., Pan CT; Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan (R.O.C.). Electronic address: pan.chienting.m@gmail.com., Wu XM; Department of Internal Medicine, Taoyuan General Hospital, University College of Medicine, Taipei, Taoyuan City, Taiwan (R.O.C.). Electronic address: ad224413@ms2.hinet.net., Chen ZW; Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan (R.O.C.). Electronic address: librajohn7@hotmail.com., Wu VC; Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (R.O.C.). Electronic address: q91421028@ntu.edu.tw., Wan CH; School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (R.O.C.). Electronic address: chwan@ntu.edu.tw., Young MJ; Baker Heart and Diabetes Institute, Prahran, Australia. Electronic address: Morag.Young@baker.edu.au., Chou CH; Department of Obstetrics and Gynecology, National Taiwan University Hospital and National Taiwan. Electronic address: joan640124@yahoo.com.tw., Lin YH; Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (R.O.C.). Electronic address: austinr34@gmail.com. |
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Jazyk: | angličtina |
Zdroj: | Translational research : the journal of laboratory and clinical medicine [Transl Res] 2022 Jan; Vol. 239, pp. 58-70. Date of Electronic Publication: 2021 Aug 16. |
DOI: | 10.1016/j.trsl.2021.08.003 |
Abstrakt: | Elevated serum aldosterone promotes arterial hypertension, cardiac hypertrophy, and diastolic dysfunction. However, the effect of elevated aldosterone levels on cardiac mitochondria remains unclear. We used primary cultures of mouse cardiomyocytes to determine whether aldosterone has direct effects on cardiomyocyte mitochondria, and aldosterone-infused mice as a preclinical model to evaluate the impact of aldosterone in vivo. We show that aldosterone suppressed mtDNA copy number and SOD2 expression via the mineralocorticoid receptor (MR)-dependent regulation of NADPH oxidase 2 (NOX2) and generation of reactive oxygen species (ROS) in primary mouse cardiomyocytes. Aldosterone suppressed cardiac mitochondria adenosine triphosphate production, which was rescued by N-acetylcysteine. Aldosterone infusion for 4 weeks in mice suppressed the number of cardiac mitochondria, mtDNA copy number, and SOD2 protein expression. MR blockade by eplerenone or the administration of N-acetylcysteine prevented aldosterone-induced cardiac mitochondrial damage in vivo. Similarly, patients with primary aldosteronism had a lower plasma leukocyte mtDNA copy number. Plasma leukocyte mtDNA copy number was positively correlated with 24-hour urinary aldosterone level and left ventricular mass index. In conclusion, aldosterone suppresses cardiac mitochondria in vivo and directly via MR activation of ROS pathways. (Copyright © 2021 Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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