Senescence and Inflamm-Aging Are Associated With Endothelial Dysfunction in Men But Not Women With Atherosclerosis
Pauline Mury, Gaël Cagnone, Olina Dagher, Florian Wünnemann, Guillaume Voghel, Mélissa Beaudoin, Mélanie Lambert, Géraldine Miquel, P. Noly, Louis P. Perrault, Michel Carrier, Nathalie Thorin‐Trescases, Jean‐Sébastien Joyal, Guillaume Lettre, Éric Thorin
Abstract
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.