FOXP3+ T-REGULATORY LYMPHOCYTES IN HYPERTENSIVE PATIENTS

Abstract

Objective: Development of coronary atherosclerosis in patients with arterial hypertension (AH) is associated with the state of chronic low-grade inflammation, but the role and function of T-regulatory (Treg) lymphocytes in this process is not yet fully elucidated. Design and method: In total 24 patients with AH of high and very high cardiovascular risk (8 men and 16 women; 61.0 (55.5; 64.00) y.o.) have been recruited in the study. All the patients underwent coronary angiography to verify the presence of coronary stenosis. Among all the recruited patients 16 individuals were characterized by at least 50% coronary stenosis. Numbers of Treg-lymphocytes were evaluated by flow cytometry according to the expression of CD4, CD25 and FoxP3 molecules. Concentrations of high-sensitive C-reactive protein (hsCRP) were measured by ELISA. Concentrations of inflammatory and anti-inflammatory cytokines were evaluated in serum and in supernatants of intact and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells’ culture by multiplex analysis. Results: Patients with coronary stenosis higher than 50% (Gr. 1) were characterized by elevated numbers of CD4+FoxP3+ Treg lymphocytes compared to the patients with minor coronary changes (Gr. 2) (3.67 (2.61; 5.37) % vs. 2.33 (1.56; 3.68) %; p = 0.047), as well as by elevated inflammatory markers, such as hsCRP (6.24 (1.98; 6.95) mg/l in Gr. 1 vs. 1.79 (1.32; 2.51) mg/l in Gr. 2; p = 0.066) and LPS-stimulated secretion of TNF-alpha (9126 (6908; 14108) pg/ml in Gr. 1 vs. 2517 (2512; 6198) pg/ml in Gr. 2; p = 0,030). Both parameters are typical to the chronic low-grade inflammation. In total group of patients concentration of serum TNF-alpha was directly related to the concentration of fasting and postprandial glucose (Rs = 0,536; p = 0,032 and Rs = 0,726; p = 0,001, respectively) as well as to the levels of HbA1c (Rs = 0,588; p = 0,035). We have revealed inverse relationships between numbers of CD25hiFoxP3+ Treg-lymphocytes and fasting levels of insulin (Rs = -0,565; p = 0,035) and HOMA (Rs = -0,666; p = 0,009). Conclusions: We have revealed the increase of Treg-lymphocytes’ numbers in patients characterized with 50% stenosis of coronary arteries, which may have compensatory role to counterbalance the state of the chronic low-grade inflammation and may be associated with the poor glycemic control in these patients.