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

Area of Science:

• Cardiovascular Science
• Molecular Biology
• Aging Research

Background:

• Coronary artery disease (CAD) shows significant sex dimorphism, with men experiencing earlier onset.
• Endothelial dysfunction, a precursor to CAD, develops approximately a decade earlier in middle-aged men compared to women.

Purpose of the Study:

• To investigate the molecular underpinnings of sex-based differences in coronary artery disease (CAD).
• To explore the endothelial cell characteristics contributing to the earlier onset of CAD in men.

Main Methods:

• Ex vivo analysis of arterial segments from patients undergoing surgery for CAD.
• Transcriptomic analysis of endothelial cells to identify molecular signatures.
• Assessment of endothelial relaxant sensitivity.

Main Results:

• Men exhibit lower endothelial relaxant sensitivity compared to women.
• Endothelial cells in men show a transcriptomic signature associated with senescence and inflammaging.
• Women's endothelial cells maintain pathways related to cellular metabolism and maintenance.

Conclusions:

• Sex-based differences in CAD prevalence are linked to distinct endothelial cell molecular profiles.
• Senescence and inflammaging in male endothelial cells may explain earlier disease onset.
• Senolytic therapies targeting cardiovascular events might have differential efficacy between sexes in CAD patients.