Aldosterone suppresses cardiac mitochondria

• Published in: Translational research : the journal of laboratory and clinical medicine 2022-01, Vol.239, p.58-70
• Main Authors: HUNG, CHI-SHENG, CHANG, YI-YAO, TSAI, CHENG-HSUAN, LIAO, CHE-WEI, PENG, SHIH-YUAN, LEE, BO-CHING, PAN, CHIEN-TING, WU, XUE-MING, CHEN, ZHENG-WEI, WU, VIN-CENT, WAN, CHO-HUA, YOUNG, MORAG J., CHOU, CHIA-HUNG, LIN, YEN-HUNG
• Format: Article
• Language: English
• Subjects: Adenoma - metabolism; Adenosine Triphosphate - metabolism; Adrenal Gland Neoplasms - metabolism; Aldosterone - metabolism; Aldosterone - pharmacology; Aldosterone - urine; Animals; Caspase 3 - metabolism; Cytochromes c - metabolism; DNA, Mitochondrial - blood; DNA, Mitochondrial - genetics; Hyperaldosteronism - genetics; Male; Mice; Mice, Inbred C57BL; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; NADPH Oxidase 2 - metabolism; Neutrophils - metabolism; Prospective Studies; Reactive Oxygen Species - metabolism; Receptors, Mineralocorticoid - metabolism
• ISSN: 1931-5244; 1878-1810
• DOI: 10.1016/j.trsl.2021.08.003

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.