Abstract
Introduction
Atherosclerosis is a multifactorial, chronic inflammatory disease that drives cardiovascular disease (CVD) and disproportionately affects postmenopausal women. Compared to premenopausal women and age-matched men, postmenopausal women experience accelerated cardiovascular dysfunction, but the mechanisms underlying this sex-specific vulnerability remain unclear.
Sleep is crucial for life, and fragmented sleep increases the risk of cardiovascular mortality. During the menopausal transition, declining estrogen levels coincide with increased sleep fragmentation (SF). Our studies demonstrate that SF accelerates age-associated vascular remodeling, leading to larger, unstable atherosclerotic plaques. The concurrent rise in CVD and SF in postmenopausal women suggests interactions between hormonal changes, sleep disruption, and vascular aging. However, fewer than 1% of preclinical cardiovascular studies utilize models of menopause, and even fewer examine how menopause-related sleep fragmentation drives atherogenesis, representing a critical gap in cardiovascular and women’s health research.
The project aimed to investigate how reproductive aging, declining estrogen, and sleep fragmentation affect atherosclerosis development in postmenopausal women.
Methods
We used a novel 4-vinylcyclohexene diepoxide (VCD) mouse model to selectively deplete ovarian follicles while preserving the ovary. After 12 weeks on a high-fat, high-cholesterol diet and SF, aortas were collected and stained with Oil Red O to quantify plaque burden. Aortic valve sections were stained with picrosirius red and MOVAT stain to assess plaque stability by comparing necrotic cores, fibrous caps, elastic fibers, and collagen.
RESULTS/
Conclusion
Our data demonstrate that SF accelerates atherogenesis in postmenopausal conditions. Ongoing studies are focused on dissecting a specific mechanism behind this increased plaque burden.