Myocardial transcriptomic and proteomic landscapes across the menopausal continuum in a murine model of chemically-induced accelerated ovarian failure

• DOI: 10.1152/physiolgenomics.00133.2024
• Publication Date: 2025-04-23T16:51:14Z
• Authors: Marissa A. Lopez-...; Vito A. Marino; Andrea C. Vazquez...; Rinku S. Skaria; Danielle K. Cannon; Christina H. Hoye...; Alice E. Solomon; Yulia Lipovka; Kevin Doubleday; Maricela Pier; Meinsung Chu; Rachel Mayfield; Samantha M. Behunin; Tianjing Hu; Paul R. Langlais; Timothy McKinsey; John P. Konhilas
• Keywords: Proteome

Risk of cardiovascular disease (CVD) in women increases with the menopausal transition. Using a chemical model (4-vinylcyclohexene diepoxide; VCD) accelerated ovarian failure, we previously demonstrated that females are more susceptible to CVD compared peri- or pre-menopausal like humans. Yet, cellular and molecular mechanisms underlying this shift susceptibility across pre- menopause continuum remain understudied. In work utilizing VCD mouse model, phenotyped signatures from hearts at each hormonally distinct stage included transcriptomic, proteomic cell biological analyses. The transcriptional profile clustered separately peri-menopausal hearts, which similarly. Proteomics also revealed hormonal clustering; grouped closely than hearts. Both proteomes transcriptomes showed similar trends genes associated atherothrombosis, contractility, impaired nuclear signaling between pre-, peri-, murine Further analysis post-translational modifications hormone-dependent shifts phosphoproteome acetylome. To further interrogate these findings, triggered pathological remodeling using angiotensin II (Ang II). Phosphorylation AMP-activated protein kinase (AMPK) histone deacetylase (HDAC) activity were found be dependent on status Ang stimulation. Finally, knock-down anti-inflammatory regulatory T cells (Treg) exacerbated II-dependent fibrosis implicating HDAC-mediated epigenetic suppression Treg activity. Taken together, unique profiles cardiac phenotype mice supporting necessity study