Aldosterone suppresses cardiac mitochondria.

Area of Science:

• Cardiovascular Biology
• Mitochondrial Medicine
• Endocrinology

Background:

• Elevated aldosterone is linked to hypertension and cardiac issues.
• The direct impact of aldosterone on cardiac mitochondria is not well understood.

Purpose of the Study:

• To investigate the direct effects of aldosterone on cardiomyocyte mitochondria.
• To evaluate aldosterone's impact on cardiac mitochondria in vivo and in patients.

Main Methods:

• Primary mouse cardiomyocyte cultures and aldosterone-infused mice models were used.
• Mitochondrial DNA (mtDNA) copy number, SOD2 expression, and ATP production were assessed.
• Mineralocorticoid receptor (MR) blockade and antioxidant treatments were employed.

Main Results:

• Aldosterone reduced mtDNA copy number and SOD2 expression via MR-dependent NADPH oxidase 2 (NOX2) and ROS generation in cardiomyocytes.
• Cardiac mitochondrial ATP production was suppressed by aldosterone but restored by N-acetylcysteine.
• In mice, aldosterone infusion decreased cardiac mitochondria, mtDNA, and SOD2; eplerenone or N-acetylcysteine prevented damage.
• Primary aldosteronism patients showed lower leukocyte mtDNA copy number, correlated with aldosterone levels and cardiac mass.

Conclusions:

• Aldosterone directly suppresses cardiac mitochondria through MR-activated ROS pathways.
• Targeting ROS or MR may protect against aldosterone-induced cardiac mitochondrial damage.
• Reduced mtDNA copy number in leukocytes may serve as a biomarker for aldosterone-induced cardiac effects.