Corticosteroids Are Essential for Maintaining Cardiovascular Function in Male Mice

Area of Science:

• Cardiology
• Endocrinology
• Molecular Biology

Background:

• Corticosteroids, including glucocorticoids and mineralocorticoids, are released by adrenal glands upon hypothalamic-pituitary-adrenal axis activation.
• The link between corticosteroids and cardiac disease is increasingly noted, but underlying mechanisms remain unclear.
• Understanding corticosteroid effects on the heart is vital for cardiovascular health.

Purpose of the Study:

• To investigate the biological effects of corticosteroids on cardiac function.
• To determine the impact of long-term adrenalectomy on heart morphology and function in mice.
• To elucidate the roles of glucocorticoids and mineralocorticoids in maintaining cardiac health.

Main Methods:

• Adrenalectomy (ADX) was performed on C57BL/6 male mice at 1 month of age.
• Mice were maintained for 3-6 months post-surgery to assess long-term effects.
• Cardiac function, morphology, gene expression, and electrocardiograms (ECGs) were analyzed.
• Hormone replacement therapy (corticosterone and/or aldosterone) was administered to ADX mice.

Main Results:

• ADX mice exhibited significantly enlarged hearts compared to controls.
• Deficits in left ventricular (LV) function and ECG abnormalities were observed in ADX mice.
• Gene expression analysis revealed aberrant pathways related to cardiac hypertrophy and arrhythmia in ADX hearts.
• Combined hormone replacement prevented cardiac abnormalities; corticosterone improved LV function but not ECGs; aldosterone improved ECGs but not LV function.

Conclusions:

• Adrenal glucocorticoids and mineralocorticoids have selective, essential roles in maintaining normal cardiac function.
• These hormones exert direct or indirect effects on the heart through their signaling pathways.
• Disruption of adrenal hormone signaling can lead to cardiac hypertrophy, dysfunction, and arrhythmias.