Associations Between Regulatory Immune Cells, Thymus Cellular Remodeling, and Vascular Aging in Advanced Coronary Atherosclerosis: A Pilot Study.

Background/Objectives: Biological aging phenotypes in coronary artery disease (CAD) include coronary atherosclerosis, vascular aging, and endothelial dysfunction. The aim of the present study was to investigate the potential links between aging phenotypes, regulatory immune cells, and features of the thymus in patients with CAD. Methods: A single-center, cross-sectional, comparative study was conducted. Patients were stratified according to the severity of coronary atherosclerosis: patients with a Gensini score ≥ 65 points and patients with a Gensini score < 65 points. Peripheral blood and thymus biopsy were obtained. Imaging flow cytometry, ELISA, and immunohistochemical analysis were used for analysis. Results: Thymic morphology ranged from total fatty involution to a preserved structure of the thymus (20-80% area in 31% of obtained samples) but was not associated with the severity of atherosclerosis. Meanwhile, patients with a Gensini score ≥ 65 had impaired thymus cellular composition compared to patients with a Gensini score < 65 points; increased frequency of CD8+ T lymphocytes and NK cells; and decreased frequency of CD4 + CD8+ T lymphocytes. In peripheral blood, the main determinants of a Gensini score ≥ 65 points were low absolute counts of eMDSCs and CD25^low Tregs with FoxP3 nuclear translocation, while advanced vascular aging was associated with elevated eMDSC absolute counts. Advanced coronary atherosclerosis was also associated with decreased numbers of endothelial progenitor cells in circulation. Conclusions: Thymus dysfunction accompanies CAD progression and is manifested in changes in cellular composition rather than morphology. In CAD patients, MDSC and Treg lymphocytes are equally involved in the progression of coronary atherosclerosis, which is aggravated by the decreased regulatory potential of the endothelium. Vascular aging represents a distinct phenotype of biological aging in CAD patients, characterized by the expansion of eMDSCs.