Cellular Senescence in the Ascending Aorta and Complexity of Coronary Atherosclerosis

TL;DR

This study shows that higher levels of senescent cells in the aorta are linked to more severe coronary artery disease in patients needing bypass surgery.

Contribution

The study identifies p16 as an independent predictor of complex coronary atherosclerosis in human vascular tissue.

Findings

p16 and p21 expression in the ascending aorta is significantly higher in patients with complex coronary lesions.

p16 remains an independent predictor of higher SYNTAX scores after multivariate analysis.

β-galactosidase expression does not correlate with coronary atherosclerosis complexity.

Abstract

Cellular senescence might have a key role in the pathogenesis of vascular aging and atherosclerosis. However, human data directly linking cellular senescence in the vascular tissue with coronary artery disease (CAD) are limited. This study aimed to investigate the relationship between the proportion of senescent cells in the ascending aorta and the complexity of CAD in patients undergoing coronary artery bypass grafting (CABG).

Ascending aortic tissue samples were obtained from 112 patients during elective or urgent CABG surgery. Expressions of p16, p21, and β‐galactosidase (β‐gal) were evaluated as cellular senescence biomarkers using immunohistochemical analysis. The complexity of coronary lesions was quantified by the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score. Patients were stratified into low and moderate‐to‐high SYNTAX score groups, and biomarker expression levels were compared between these subgroups.

The proportion of p16‐positive cells in the ascending aorta was significantly higher in patients with moderate‐to‐high SYNTAX scores, by both percentage (p = 0.015) and staining grade (p = 0.035). Similarly, p21 expression was elevated in the moderate‐to‐high SYNTAX group (percentage, p = 0.015; grade, p = 0.030). β‐gal expression showed no significant association with CAD complexity. In multivariate logistic regression analysis, p16 expression remained an independent predictor of higher SYNTAX score (OR: 1.016; 95% CI: 1.000–1.031; p = 0.047).

Increased expression of p16 and p21 in ascending aortic tissue is significantly associated with higher coronary atherosclerosis complexity in patients undergoing CABG. Among these biomarkers, p16 serves as an independent predictor of complex CAD, highlighting its potential role in vascular aging and atherosclerosis progression.

Figures