Senescence and Inflamm-Aging Are Associated With Endothelial Dysfunction in Men But Not Women With Atherosclerosis.

Coronary artery disease (CAD) is more prevalent in men than in women, with endothelial dysfunction, prodromal to CAD, developing a decade earlier in middle-aged men. We investigated the molecular basis of this dimorphism ex vivo in arterial segments discarded during surgery of CAD patients. The results reveal a lower endothelial relaxant sensitivity in men, and a senescence-associated inflammaging transcriptomic signature in endothelial cells. In women, cellular metabolism and endothelial maintenance pathways are conserved. This suggests that senolytic therapies to reduce risk of cardiovascular events in women with CAD may not be as effective as in men.
Competing Interests: This work was supported by the Canadian Institutes of Health Research grant (PJT-162446 to Dr Thorin), and the Foundation of the Montreal Heart Institute (Dr Thorin). Drs Mury and Lambert have been supported by the postdoctoral program of the Fonds de la recherche du Québec. Dr Cagnone has received support from the Vision Health Research Network. Dr Dagher has received support from the Canadian Institutes of Health Research (grant FBD-183276). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(© 2024 The Authors.)