Age-Associated Changes in the Molecular Profile of Endothelial Dysfunction

Highlights The molecular profile of dysfunctional endothelium in coronary artery disease is characterized by increased concentrations of the endothelial glycocalyx components SDC1 and ESM1, pro-inflammatory cell adhesion molecules ICAM1, VCAM1, and E-selectin, VEGFR2, and vWF, and decreased concentrations of SDC2, ENG, and ET-1 compared with apparently healthy individuals. Age-associated changes in the molecular profile are predominantly observed in individuals with normal endothelial function, whereas in coronary artery disease, most of the studied markers show no association with age, suggesting a predominant influence of endothelial dysfunction on their concentrations. In coronary artery disease, the relationships between endothelial glycocalyx components, markers of pro-inflammatory activation, and angiogenic regulation are altered, indicating changes not only in the concentrations of individual markers but also in the relationships among molecular markers of dysfunctional endothelium. Aim. To characterize age-associated changes in the molecular profile of endothelial dysfunction in patients with coronary heart disease (CHD) and apparently healthy individuals based on a comparative analysis of molecular marker concentrations, their interrelationships, and associations with age. Methods. The study included 31 apparently healthy volunteers (mean age, 34 years) and 106 patients with CAD (mean age, 64.5 years) who underwent on-pump coronary artery bypass graft surgery. The concentrations of the endothelial glycocalyx components SDC1, SDC2, SDC4, and ESM1; cell adhesion molecules ICAM1, VCAM1, and E-selectin; constitutive endothelial cell receptor markers VEGFR2 and ENG; as well as vWF and ET-1 were measured by enzyme-linked immunosorbent assay. The concentrations of the studied markers were compared between the groups, and correlation analysis was performed to assess their associations with age and relationships with each other. Results. Patients with CAD had higher concentrations of SDC1, ESM1, ICAM1, VCAM1, E-selectin, VEGFR2, and vWF and lower concentrations of SDC2, ENG, and ET-1 compared with apparently healthy individuals, whereas SDC4 concentrations did not differ between the groups. In the overall sample, age positively correlated with ICAM1 (r = 0.4573), SDC1 (r = 0.3530), and ESM1 (r = 0.3781) concentrations and negatively correlated with ET-1 (r = −0.5588). However, none of the markers showed an association with age that was consistently observed in both groups and in the overall sample. Among apparently healthy individuals, age correlated with VCAM1 (r = 0.4122) and vWF (r = −0.5420), whereas most age-related associations were absent in patients with CAD. Analysis of relationships between the markers demonstrated correlations between glycocalyx components, molecules involved in pro-inflammatory activation, and markers of angiogenic regulation in both groups; however, the strength and pattern of individual relationships differed depending on the functional state of the endothelium. Conclusion. CAD is associated with a distinct endothelial molecular profile characterized by alterations in glycocalyx components, pro-inflammatory activation, angiogenic regulation, and hemostasis. Age-associated changes in the studied markers are predominantly observed in individuals with normal endothelial function, whereas most age-related associations are absent in CAD. These findings suggest that endothelial dysfunction becomes a dominant factor determining the endothelial molecular profile in CAD, thereby reducing the independent contribution of age.