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

Pauline Mury; Gael Cagnone; Olina Dagher; Florian Wünnemann; Guillaume Voghel; Melissa Beaudoin; Mélanie Lambert; Géraldine Miquel; Pierre-Emmanuel Noly; Louis P Perrault; Michel Carrier; Nathalie Thorin-Trescases; Jean-Sébastien Joyal; Guillaume Lettre; Eric Thorin

doi:10.1016/j.jacbts.2024.06.012

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

JACC Basic Transl Sci. 2024 Sep 4;9(10):1163-1177. doi: 10.1016/j.jacbts.2024.06.012. eCollection 2024 Oct.

Authors

Pauline Mury^{1

2}, Gael Cagnone³, Olina Dagher^{1

2

4}, Florian Wünnemann¹, Guillaume Voghel⁵, Melissa Beaudoin¹, Mélanie Lambert^{1

2}, Géraldine Miquel¹, Pierre-Emmanuel Noly^{1

6}, Louis P Perrault^{1

6}, Michel Carrier^{1

6}, Nathalie Thorin-Trescases¹, Jean-Sébastien Joyal^{3

7

8}, Guillaume Lettre^{1

9}, Eric Thorin^{1

6}

Affiliations

¹ Montreal Heart Institute Research Center, University of Montreal, Montreal, Quebec, Canada.
² Department of Pharmacology and Physiology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
³ University Hospital Sainte Justine Research Center, University of Montreal, Montreal, Quebec, Canada.
⁴ Department of Cardiac Sciences, Libin Cardiovascular Institute, Calgary, Alberta, Canada.
⁵ Department of Family Medicine and Emergency Medicine, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
⁶ Department of Surgery, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
⁷ Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
⁸ Department of Ophthalmology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
⁹ Department of Medicine, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.

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.

Keywords: coronary artery disease; endothelium-dependent relaxation; inflammaging; sex-dimorphism.