Female Cardioprotection in a Mouse Model of Alcohol-Associated Cardiomyopathy
Joshua M Edavettal1, Meagan Donovan1, Nicholas R Harris1
1LSU Health Sciences Center, Department of Physiology, New Orleans, LA 70112, USA.
Cells
|November 13, 2025
Summary
Chronic alcohol misuse causes heart disease. This study found alcohol-induced heart dysfunction in males but not females, with no significant mitochondrial changes in either sex, suggesting hormonal protection in females.
Area of Science:
- Cardiology
- Toxicology
- Mitochondrial Biology
Background:
- Chronic alcohol misuse is a primary cause of non-ischemic dilated cardiomyopathy.
- The molecular mechanisms and sex-specific differences in alcohol-associated cardiomyopathy (ACM) remain incompletely understood.
- Mitochondrial dysfunction is implicated in heart disease, but its role in ACM requires further clarification.
Purpose of the Study:
- To investigate sex differences in cardiac dysfunction and mitochondrial function following chronic plus binge ethanol consumption.
- To explore the molecular mechanisms underlying alcohol-induced cardiotoxicity, focusing on sex-specific susceptibility.
- To determine the impact of ethanol exposure on mitochondrial respiration, ATP production, and oxidative stress.
Main Methods:
- A preclinical model using male and female C57BL/6J mice subjected to 30 days of ethanol or control liquid diet with two binge episodes.
- Cardiac morphology and function assessed via echocardiography and pressure-volume catheterization.
- Mitochondrial function evaluated using Seahorse XF analysis, ATP luminescence, and AmplexTM Red fluorescence assays.
Main Results:
- Ethanol consumption induced significant cardiac dysfunction and increased inflammatory and fibrotic markers in males, but not in females.
- No significant alterations in mitochondrial respiration, ATP production, collagen expression, or oxidative stress were observed in either sex.
- These findings highlight sex-specific cardiac responses to chronic plus binge ethanol exposure.
Conclusions:
- Chronic plus binge ethanol consumption leads to distinct cardiac outcomes between male and female mice, with males exhibiting significant dysfunction.
- Mitochondrial function appears preserved despite ethanol-induced cardiac effects, suggesting other pathways are involved in ACM.
- Ovarian hormones may play a cardioprotective role in females, warranting further investigation into their mechanisms against alcohol-related heart damage.
