Here find an interesting review of the sex differences observed in the development of atherosclerosis in humans. This condition, in which fatty plaques develop to narrow arteries, is the leading cause of mortality in our species. Plaques rupture to cause blockage of a downstream vessel and a heart attack or stroke. The authors here focus on differences between the sexes in cellular senescence and inflammation in the vasculature. Men tend to bear a greater burden of both of these mechanisms. The implication is that senolytic and anti-inflammatory therapies will benefit men more than women in the specific context of atherosclerotic cardiovascular disease.
The prevalence of coronary artery disease (CAD) is higher in men than in women, but the underlying molecular basis for this sexual dimorphism are poorly understood. There is a consensus on the protective role of estrogens and CAD risk increasing following menopause. Likewise, men develop lipid-rich plaques, whereas women are more likely to develop fibrous plaques with a unique transcriptomic and proteomic signatures in the plaque. Otherwise, presentation of oxidative stress and inflammation may differ between women and men but are inconsistent.
In healthy humans, aging is associated with a progressive endothelium-dependent dilatory decline, which appears 10 years earlier in men than in women and is highly predictive of future cardiovascular events. In recent years, research has established that age-related accumulation of senescent cells could cause chronic low-grade cold inflammation, also known as inflammaging, through the release of the senescence-associated secretory phenotype (SASP). Because SASP involves a range of proinflammatory factors with important paracrine and autocrine effects on cell and tissue biology, inflammaging could promote cardiovascular disease (CVD).
We prospectively collected distal segments of lesion-free internal thoracic arteries during coronary artery bypass graft surgeries from both men and women. Our data show that endothelial dysfunction is more pronounced in men compared to women. Importantly, using single-nuclei transcriptomics, senescent and inflammatory transcriptomic signatures suggestive of the inflammaging were only identified in male endothelial cells, not in female endothelial cells. Therefore, senescence-associated endothelial dysfunction may contribute to atherogenesis in men.
Link: https://doi.org/10.1016/j.jacbts.2024.06.012
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