Aldosterone suppresses cardiac mitochondria
Copyright © 2021 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:239 |
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| Enthalten in: |
Translational research : the journal of laboratory and clinical medicine - 239(2022) vom: 01. Jan., Seite 58-70 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hung, Chi-Sheng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.01.2022 Date Revised 26.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.trsl.2021.08.003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Hung, Chi-Sheng |c (啟盛) 628401 |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Aldosterone suppresses cardiac mitochondria |
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| 500 | |a Date Revised 26.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a Receptors, Mineralocorticoid |2 NLM | |
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| 700 | 1 | |a Chang, Yi-Yao |e verfasserin |4 aut | |
| 700 | 1 | |a Tsai, Cheng-Hsuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Che-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Shih-Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Bo-Ching |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Chien-Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xue-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zheng-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Vin-Cent |e verfasserin |4 aut | |
| 700 | 1 | |a Wan, Cho-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Young, Morag J |e verfasserin |4 aut | |
| 700 | 1 | |a Chou, Chia-Hung |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Yen-Hung |e verfasserin |4 aut | |
| 700 | 0 | |a TAIPAI Study Group |e verfasserin |4 aut | |
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