X inactivation regulates lymphocyte induced cardiac remodeling

After menopause, women lose the protective effect of female hormones and experience increased risk of adverse cardiac remodeling following myocardial infarction (MI). This may be due in part to the deleterious effects of genes encoded on the X chromosome. On average, 15% of genes located on the X chromosome escape inactivation in women, resulting in over expression. We hypothesize that with age T-cells escape X-chromosome inactivation (XCI), thus exacerbating the inflammatory response and resulting in adverse post-MI remodeling in women. We will use 2 aims to delineate a mechanism defining age effects on XCI and how this in turn influences T-cell mediated post-MI remodeling. Aim 1 will test the hypothesis that older females have an increased number of T-cells that escape XCI and exacerbate monocyte recruitment and activation post-MI. Aim 2 will test the hypothesis that female mice with T-cells that have escaped XCI will have adverse remodeling and decreased post-MI survival. Our understanding of sex differences especially the influence of sex chromosomes during post-MI remodeling and development of heart failure is lacking. The information obtained from the proposed experiments will have direct implications for medical management of women post-MI. Myocardial infarction as induced in C57Bl6/J female mice by permanent occlusion of the left anterior descending artery ligation. At post-MI Day 5, cells were isolated from the infarct zone of young (3-5 months) and old (15-17 months old) and run for scRNA sequencing.