We studied dynamics of content of subpopulation of lymphocytes including regulatory and effector T-lymphocytes as well as concentration of soluble form of interleukine-2 receptor (sCD25) in peripheral blood of patients after coronary stenting (CS) with implantation of stents with rapamycin covering (SRC). We included into the study 62 patients with stable effort II-III functional class angina. Coronary angiography (CA) was carried out in all, CS with implantation of 1 - 2 SRC - in 42 patients. Blood samples were taken before CA/CS, in 24, 48 hours, 7 days, 1 and 3 months after intervention. Content of T-, helper and cytotoxic T-cells, -, NK-, NKT-cells, activated effector T-lymphocytes (CD4+CD251owCD127high) and regulatory T-lymphocytes (CD4+CD25highCD1271ow) were measured by direct immunofluorescence and flow cytometry. CD4+ lymphocytes were isolated from mononuclear cell fraction of donor blood by magnetic separation. Content of regulatory T-lymphocytes in culture were determined by expression of a specific marker FOXP3+. Concentration of sCD25 was measured by chemiluminescent method. It was shown that content of main subpopulations of lymphocytes in blood changed after CS or CF. Blood content of regulatory T-lymphocytes and sCD25 significantly increased after 7 days and 1 month after CS but not after CA. Plasma sCD25 concentration correlated with content of regulatory T-lymphocytes in 1 month after SRC implantation. During cultivation of CD4+ lymphocytes in the presence of rapamycin we noted antiproliferative effect relative to FOXP3-cells and accumulation of regulatory +-lymphocytes. Thus implantation of SRC in coronary arteries leads to increase of number of circulating regulatory T-lymphocytes and blood concentration of sCD25. Changes of these parameters after CS can reflect peculiarities of local and systemic reaction arising in response to introduction of stent with drug covering and be significant for assessment of prognosis of the disease.

The effects of the synthetic monocyte chemotactic protein-1 (MCP-1) peptide fragment 65–76 (peptide X) on the development of neointima after balloon injury to the carotid artery were studied. The agent was given i.m. at a dose of 33 µg/kg once daily for 28 days after balloon injury. Animals given peptide showed significant suppression of neointima growth 4 and 7 days after lesioning, as indicated by morphometric analysis of sections of lesioned arteries. On days 14 and 28, there were no significant differences in neointima formation in rats given and not given peptide. Peptide administration was not accompanied by any changes in C-reactive peptide concentrations, leukocyte counts, or the population composition of peripheral blood lymphocytes. Use of synthetic peptide X as an inhibitor of leukocyte migration during angioplasty may, along with traditional treatments, decrease the risk of restenosis.

The content of marker foxp3 of regulatory T cells and chemokines in atherosclerotic plaques of human coronary arteries was measured by the polymerase chain reaction. In vitro migration of regulatory CD4+CD25+foxp3+ cells in the CD4+ lymphocyte population from healthy donors was studied after treatment with chemokines I-309, IP-10, and SDF-1. mRNA for the factor foxp3 and chemokines SDF-1, I-309, and MIP-1β were found in the majority of samples from atherosclerotic plaques. SDF-1 induced maximum migratory response of CD4+CD25+foxp3+ cells.

AIM:To investigate the effects of coronary stenting with rapamycin-eluting stents on parameters of cell immunity.METHODS:26 patients (group 1) with stable coronary heart disease and angiographically proved coronary stenosis underwent stenting with rapamycin-eluting stents. The control group (group 2) consisted of 6 patients: 4 patients underwent diagnostic coronaroangiography, I patient got a bare metal stent and in 1 patient angioplasty was unsuccessful. Blood samples were obtained before and 1 month after the intervention. The quantity of activated (CD4+CD25low+) and regulatory (CD4+CD25high+) T cells was measured by direct immunofluorescence and flow cytometry. Plasma concentration of IL-10 was determined by ELISA.RESULTS:In group 1 the percentages of CD4+CD25high+ regulatory T-cells increased significantly one month after stenting, while in group 2 no difference in regulatory T-cell levels before and after the intervention was observed. No changes in total number of leukocytes, relative levels of lymphocytes, CD4+ T-cells, activated CD4+CD25+low T-cells and IL-10 plasma concentration before and after the procedure were detected in both groups.CONCLUSION:Rapamycin-eluting stent implantation is associated with a significant increase of circulating CD4+CD25high+ regulatory T-cell level.

Influence of synthetic fragment 65-76 of monocyte chemoattractant protein-1 (MCP-1) (peptide X) on development of neointima after balloon injury of carotid artery was investigated. Peptide X was introduced intramuscularly, 33 pg/kg, daily during 28 days after balloon injury. In days 4 and 7 after intervention, in animals receiving peptide X in comparison with control animals a substantial decrease of neointimal growth was observed. On 14 and 28 days there, was no significant difference in neointima development in rats with and without peptide treatment. Injections of peptide X did not after the C-reactive protein concentration, leukocyte number and lymphocyte subpopulations in peripheral blood. Peptide X treatment along with traditional therapy may be effective in preventing restenosis after angioplasty.