# Female Cardioprotection in a Mouse Model of Alcohol-Associated Cardiomyopathy

## TL;DR

This study finds that female mice are protected from alcohol-induced heart damage, while males show significant cardiac dysfunction and inflammation.

## Contribution

The study reveals sex-specific differences in alcohol-associated cardiomyopathy and suggests a potential role for ovarian hormones in female cardioprotection.

## Key findings

- Male mice showed cardiac dysfunction and increased inflammatory and fibrotic markers after ethanol exposure.
- Female mice exhibited no significant cardiac or mitochondrial changes following alcohol exposure.
- Mitochondrial function and oxidative stress were unaffected in both sexes despite ethanol feeding.

## Abstract

Chronic alcohol misuse is the leading cause of non-ischemic dilated cardiomyopathy, and the molecular mechanisms underlying the development of alcohol-associated cardiomyopathy (ACM), particularly regarding sex-specific susceptibility and mitochondrial contributions, are not fully known. In this study, we utilized a preclinical model of chronic + binge ethanol consumption to investigate sex differences in disease severity and mitochondrial function. Male and female C57BL/6J mice were fed ethanol or control liquid diets for 30 days, with 2 binge episodes on days 10 and 30. Cardiac morphology was assessed via echocardiography and cardiac function via left ventricular pressure–volume catheterization. Mitochondrial function was evaluated ex vivo using Seahorse XF analysis, ATP luminescence, and AmplexTM Red fluorescence in isolated ventricular mitochondria. Ethanol feeding induced significant cardiac dysfunction and increased transcriptional expression of inflammatory and fibrotic markers in males, while these effects were not seen in females. Despite these sex-specific cardiac effects, mitochondrial respiration, ATP production, collagen protein expression, and oxidative stress were not significantly altered following alcohol exposure in either sex. Further investigation is warranted to assess the potential role of ovarian hormones in this female cardioprotection against chronic + binge ethanol.