Myocardial transcriptional, and proteomic landscapes across the pre-menopausal, peri-menopasual, and menopasual continuum

More women than men have died from heart disease over the last 20-25 years, with morbidity and mortality rising in women after menopause supported to be result of decreased circulating estrogen. Current literature lacks an understanding of the cellular and molecular mechanisms that capture the shift in susceptibility to cardiovascular disease (CVD) during the menopausal transition from pre- to peri- to menopause. Therefore, through use of a chemical model (4-vinylcyclohexene diepoxide; VCD) of ovarian failure, which allows us to preserve the peri-menopause state, we performed transcriptomic and proteomic analysis on post-mortem heart tissue. In general, pre-, peri-, and menopausal hearts clustered more closely (most similar) within each experimental group and perimenopausal hearts clustered more closely with premenopausal hearts than menopausal hearts (least similar). Both proteomes and transcriptomes showed similar trends in genes associated with atherothrombosis, contractility, and impaired nuclear signaling between pre-, peri-, and menopausal hearts. From this, we emphasized a menopause and angiotensin II (AngII) effect on AMP-activated protein kinase (AMPK) signaling and histone deacetylase (HDAC) activity where we found both an estrogen- and pathologic-dependent increase in phosphorylation of AMPK and decrease in class I HDAC activity. Additionally, we found a menopause-dependent decrease in class IIa HDAC activity and increase in class IIb activity. These findings suggest unique changes in pre-, peri-, and menopausal mice indicative of metabolic reprogramming and adverse cardiac remodeling with loss of estrogen. Overall design: To investigate the menopasual pathogenic heart and the progression of disease from high estrogen production to low estrogen production, buy utilizing the VCD model in mice. performed RNA seq profiling on 12 hearts , 4 for each group premenopausal , perimenopausal, and menopausal hearts ( LV and RV). comparative RNA seq profiling for comparing each group to one another using one-way anova anlaysis.