CD4(+)CD25(high)CD127(low) regulatory T cells in patients with stable angina and their dynamics after intracoronary sirolimus-eluting stent implantation

Rapamycin contributes to the expansion of regulatory T cells (Tregs) in vitro. We investigated CD4(+)CD25(high)CD127(low) Treg level dynamics as well as the major parameters of cell immunity and sCD25 and highly sensitive C-reactive protein (hsCRP) concentrations in the blood of patients after coronary stenting (CS) with sirolimus (rapamycin)-eluting stents (SES; n = 43). The relation between initial Treg values and the severity of coronary atherosclerosis was observed. Treg and sCD25 levels were increased 1 month after CS versus baseline values and versus data in the control group (coronary angiography [CA], n = 20). A positive correlation between Treg and sCD25 levels was reported, whereas no relation was observed with the length of SES implanted. HsCRP level was increased during the first 7 days and returned to baseline values 1 month after CS/CA. Treg content is lower in patients with multivessel CAD. Elevated levels of Tregs and sCD25 after SES implantation might occur because of the immunomodulating effect of rapamycin.     

Urokinase plasminogen activator system in humans with stable coronary artery disease

1. The present study compares plasma urokinase plasminogen activator (uPA) peptide levels, plasma plasminogen inhibitor (PAI-1) activity and urokinase receptors (uPAR) on peripheral blood monocytes of patients with stable coronary artery disease (SCAD) and healthy volunteers. 2. Urokinase plasminogen activator levels were analysed by ELISA and PAI-1 activity was determined by a plasmin generation method using the chromogenic substrate S2390. Relative uPAR numbers and the adhesion molecules CD11b/CD18 on peripheral blood monocytes were estimated using specific antibodies and flow cytometry. 3. Patients with SCAD were found to have higher plasma uPA peptide levels than age-matched healthy subjects (10.40 +/- 0.99 vs 8.25 +/- 0.53 pmol/L, respectively; P < 0.05). 4. Plasma PAI-1 activity was also higher in patients with SCAD than in healthy subjects (13.6 +/- 2.5 vs 5.2 +/- 1.0 IU/mL, respectively; P < 0.05). 5. Relative uPAR and CD11b/CD18 adhesion molecules were similar on peripheral blood monocytes of patients with SCAD and in healthy subjects. 6. The data indicate a pattern of expression/activity of uPA and PAI-1 in patients with SCAD suggestive of an impaired fibrinolytic ability.     

Monocyte integrin expression and monocyte-platelet complex formation in humans with coronary restenosis

1. In the present study, we sought to determine whether patients with restenosis after coronary stenting possess increased monocyte reactivity, as manifested by a higher level of adhesion molecule expression and an enhanced propensity to form monocyte-platelet aggregates after activation in vitro. 2. Anti-coagulated peripheral venous blood from 24 patients, 10 with and 14 without angiographically verified restenosis, was obtained. Leucocyte antigen expression and the number of leucocyte-platelet complexes were measured by flow cytometry after activation in whole blood. 3. Surface integrin Mac-1 (CD11b/CD18) and VLA-4 (CD49d/ CD29) expression on monocytes and the relative number of monocyte-platelet complexes after in vitro activation were significantly elevated in patients with restenosis compared with patients without restenosis (fluorescence intensities of 1425 +/- 76 vs 1195 +/- 71, 87 +/- 7 vs 65 +/- 6 and 47 +/- 4 vs 29 +/- 3% for for Mac-1, VLA-4 and monocyte-platelet complexes, respectively; P < 0.05 for each parameter). 4. The results suggest that restenosis is associated with increased monocyte VLA-4 and Mac-1 integrin expression and monocyte-platelet complex formation, which can be revealed after activation in vitro.     

Changes in the concentration of monocytic chemotaxic protein-1 in patients with unstable angina treated with arixtra

The time course of inflammatory reaction markers in the blood of patients with unstable angina was studied during therapy including arixtra. Plasma concentration of monocytic chemotaxic protein-1 (MCP-1) decreased on days 2 and 3 in patients receiving arixtra and a trend to an increase in MCP-1 concentration was observed on day 7 after the drug was discontinued. After 1 month, MCP-1 level decreased in all patients. The concentration of highly sensitive C-reactive protein also decreased 1 month after the disease onset; no changes in the concentrations of IL-8 and IL-2 receptor α-subunit were detected during these periods. It seems that arixtra is characterized by an anti-inflammatory effect manifesting by reduction of plasma chemokine MCP-1 concentration.     

Immunoinflammatory Aspects of Parkinson’s Disease

Neuroscience and Behavioral Physiology - This review analyzes immunological impairments in Parkinson’s disease (PD). We present data on neuroinflammation, with which cell degeneration in the...     

Expression of Markers of Regulatory CD4<Superscript>+</Superscript>CD25<Superscript>+</Superscript>foxp3<Superscript>+</Superscript> Cells in Atherosclerotic Plaques of Human Coronary Arteries

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.     

Synthetic peptide fragment (65�C76) of monocyte chemotactic protein-1 (MCP-1) inhibits MCP-1 binding to heparin and possesses anti-inflammatory activity in stable angina patients after coronary stenting

Objective and design

The peptide from C-terminal domain of MCP-1 (Ingramon) has been shown to inhibit monocyte migration and possess anti-inflammatory activity in animal models of inflammation and post-angioplasty restenosis. Here, we investigate the effect of Ingramon treatment on blood levels of acute-phase reactants and chemokines in patients after coronary stenting and the mechanisms of Ingramon anti-inflammatory activity.

Subjects

Eighty-seven patients with ischemic heart disease (IHD) who faced the necessity of coronary angiography (CA) were enrolled. In 67 patients, one-stage coronary stenting was performed; 33 of them were treated with Ingramon in addition to standard therapy. Twenty patients underwent CA only.

Methods

High-sensitivity C-reactive protein (hsCRP) and fibrinogen blood levels were detected routinely. The chemokine concentration in plasma was measured by enzyme-linked immunosorbent assay (ELISA) or cytometric bead array-based immunoassay. Intracellular Ca²⁺ levels and cell surface integrin exposure were assayed by flow cytometry. MCP-1 dimerization was studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). MCP-1?Cheparin binding was assessed with a biosensor and ELISA.

Results and conclusions

Ingramon treatment was accompanied by less pronounced elevation of hsCRP and fibrinogen levels and decreased MCP-1 concentration in plasma in patients after coronary stenting. Ingramon had no effect on MCP-1 interaction with cell receptors or MCP-1 dimerization, but inhibited MCP-1 binding to heparin. The anti-inflammatory activity of the peptide may be mediated by an impaired chemokine interaction with glycosaminoglycans.