Abstract Body: Introduction:
Myocardial infarction (MI) induces a robust inflammatory response essential for cardiac repair, yet dysregulated inflammation can exacerbate damage. Emerging evidence suggests that epigenetic modifications, including DNA methylation and histone modifications, play a critical role in modulating inflammatory pathways. However, how these mechanisms differ between sexes and contribute to disparities in MI outcomes remains poorly understood. This study aims to identify sex-specific epigenetic signatures regulating post-MI inflammation and assess their impact on recovery.

Hypothesis:
Sex differences in post-MI inflammation are driven by distinct epigenetic modifications, contributing to divergent cardiac repair outcomes.

Methods:
40 male and female mice undergo MI or sham surgery via left anterior descending (LAD) coronary artery ligation. Cardiac tissue is collected at multiple post-MI time points for epigenetic & inflammation analyses, including DNA methylation profiling, histone modification assays, RT-qPCR, western blotting, and immunohistochemistry. Functional outcomes are assessed via echocardiography to correlate epigenetic changes with cardiac function.

Results:
Preliminary data suggest sex-specific differences in histone methylation and acetylation at key inflammatory gene loci post-MI. Female mice exhibit reduced chemokines such as CXCL1 in serum and RNA post-MI compared to male mice. In RNA, 15 epigenetic enzymes are differentially expressed, including CIITA and SETDB2, which are upregulated in male mice 3 days after MI compared to female mice. ELISAs also suggest that H3ser28P and H3K9me2/3 modification percentages increase with MI in males and females. Further analysis is ongoing to validate these findings and determine mechanistic pathways.

Conclusions:
This study provides novel insights into the role of epigenetic regulation in sex-based differences in post-MI inflammation. Understanding these mechanisms may lead to the development of sex-specific therapeutic strategies to improve MI outcomes.