Circulating FoxP3+ T-lymphocytes in chronic coronary artery disease: Associations with the severity of atherosclerosis and lipid metabolism

Abstract

Introduction. The transcription factor forkhead box protein P3 (FoxP3) is a major regulator of T-regulatory (Treg) lymphocytes and may be expressed in T-conventional (Tconv) lymphocytes at the stage of their activation. The aim of the present study was to evaluate the quantities and features of FoxP3+ Tconv and Treg lymphocytes and their relationships with the parameters of lipid metabolism in patients with chronic coronary artery disease (CAD) depending on the severity of coronary atherosclerosis.Material and Methods. The study comprised 14 patients (8 men and 6 women) aged 66.5 ± 9.0 years with verified chronic CAD. All the patients underwent coronary angiography and assessment of atherosclerosis severity by calculation of Gensini Score index (GS). Patients were divided into the following groups: group 1 had GS < 20; group 2 had GS ≥ 20. The absolute and relative counts of FoxP3+ Treg and Tconv lymphocytes and degree of FoxP3 nuclear translocation were evaluated in all patients by imaging flow cytometry. Concentrations of insulin, proprotein convertase subtilisin/kexin type 9 (PCSK9), and sortilin were assessed using enzyme-linked immunosorbent assay. Parameters of glucose metabolism and serum lipid spectrum were determined by the standard methods.Results. Counts of Treg and Tconv lymphocytes did not differ between groups of patients with different severity of atherosclerosis. However, patients with GS ≥ 20 had lower intensity of nuclear FoxP3 fluorescence in Treg and Tconv lymphocytes. GS index in the entire group of CAD patients tended to be negatively associated with the fluorescence intensity of FoxP3 in the nuclei of Treg (rs = –0.476) and Tconv lymphocytes (rs = –0.526). Multiple correlations existed between the quantitative and qualitative parameters of FoxP3+ Treg and FoxP3+ Tconv lymphocytes and metabolic parameters such as concentrations of PCSK9, sortilin, apolipoprotein B, and triglycerides/HDL cholesterol ratio.Conclusion. FoxP3 fluorescence intensity in the nuclei of T conventional lymphocytes was more sensitive marker of immunoregulatory imbalance in chronic CAD compared to counts of FoxP3+ T cells in the peripheral blood, which remained nearly unaltered with the increase in atherosclerosis severity. At the same time, markers of lipid metabolism were tightly associated with both quantitative and qualitative features of FoxP3+ T-lymphocytes.