Effect of Atorvastatin Therapy on the Level of CD34+CD133+CD309+ Endothelial Progenitor Cells in Patients with Coronary Heart Disease.

In 58 patients with coronary heart disease, the count of CD34+CD133+CD309+ endothelial progenitor cells in the blood was determined and the dynamics of the content of endothelial progenitor cells, angiogenic growth factors, and lipid parameters over 3 months of atorvastatin therapy was analyzed. Atorvastatin was administered in daily doses of 10 mg (26 patients) and 40 mg (32 patients). Control group comprised 15 healthy volunteers. In patients with coronary heart disease, the count of endothelial progenitor cells was lower by 4 times, the level of VEGF was higher by 52%, and the level of endostatin was lower by 13% than in healthy volunteers. Atorvastatin therapy significantly reduced the levels of VEGF (by 11%), C-reactive protein (by 26%), total cholesterol (by 30%), LDL cholesterol (by 35%), and triglycerides (by 18%); the levels of endostatin, MCP-1, and HDL cholesterol remained unchanged. The count of endothelial progenitor cells increased significantly by 72% irrespectively on the statin dose, but the changes were more pronounced in patients with lower initial endothelial progenitor cell counts and in patients with more drastic decrease in LDL cholesterol.

[Detection of Autoantibodies Against the 1-Adrenergic Receptor in the Sera of Patients via the Competitive cell-Based Enzyme Linked Immunosorbent Assay].

OBJECTIVE: This study aimed to assess the level of anti-1-adrenergic receptor autoantibodies in patients with ventricular arrhythmias with no signs of organic heart disease and with presence of cardiovascular pathology in comparison with a group of healthy volunteers. MATERIAL AND METHODS: The study included 44 patients with ventricular arrhythmias with no signs of organic heart disease ("idiopathic"), 34 patients with diagnosed dilated cardiomyopathy (DCM) of inflammatory origin, 35 patients with coronary heart disease and ventricular arrhythmias, 12patients with coronary heart disease with no ventricular arrhythmias, and 19 healthy volunteers (control group). The level of autoantibodies against the 1-adrenergic receptor was determined by the developed competitive cell-based enzyme-linked immunosorbent assay (ELISA) and by the standard ELISA using peptides corresponding to the second extracellular loop of the 1-adrenergic receptor. RESULTS: Elevated level of autoantibodies detected by a competitive cell-based ELISA was observed in 62% of patients with DCM compared to 21% of healthy volunteers (p=0.0006). In patients with "idiopathic" ventricular arrhythmias, the level of 1-adrenergic receptor autoantibodies was lower than in healthy subjects (p=0.003). Coronary heart disease patients with or without ventricular arrhythmias exhibited no differences from the control group. The number of significantly positive signals in peptide-based ELISA did not exceed 10% in any of the groups. No correlation between the data from competitive cell-based ELISA and peptide-based ELISA was found. CONCLUSIONS: This study demonstrated that competitive cell-based ELISA technique can be applied for detection of 1-adrenergic receptor autoantibodies. The results in DCM patients generally correspond to the expected. Decreased level of autoantibodies in patients with "idiopathic" ventricular arrhythmias indicates that this disease is related to changes in the immune system. Such relation is not observed in the case of coronary heart disease patients.

[Radioligand Method of Assessment of ß-Adrenoceptor's Activity on Human T-Lymphocytes].

We proposed a new method of evaluation of beta-receptor's activity on the surface of human T-lymphocytes based on the radioligand method. Optimal conditions for evaluation of specific binding to ß2-adrenoceptors of 0.5 fmol ligand per 1 million cells using [125I]-cyanopindolol were found. The possibility of using of ß2-adrenoceptor's activity assessment in clinical settings was demonstrated on human T-lymphocyte.

[Estimation of immune response parameters in patients with frequent premature ventricular contractions without signs of organic pathology of the cardiovascular system].

AIM: To study the specific features of an immune response and the role of infectious pathogens in the occurrence, development, and maintenance of ventricular ectopic activity in patients without signs of organic disease of the cardiovascular system (CVS). SUBJECTS AND METHODS: The investigation enrolled 91 patients (27 men and 64 women with a mean age of 36.5 +/- 11.5 years) with premature ventricular contractions (PVC) without signs of organic CVS pathology. A control group comprised 31 healthy volunteers. In addition to standard physical examination, a study of N-terminal pro-brain natriuretic peptide (NT-proBNP) and cellular and humoral immune parameters was performed and the serological and molecular genetic markers of infections were determined in all the patients. RESULTS: The persons with PVC, as compared to the control group, were recorded to have a higher NT-proBNP level (49.2 pg/ml versus 25.4 pg/ml; p = 0.001) accompanied by an increase in both the total number of PVC and the number of coupled PVC and the episodes of ventricular tachycardia. They were also found to have elevated CD3(+)HLA-DR+ (2.4% versus 1.56%) and CD3(+)CD95+ (27.6% versus 18.8%) counts (p = 0.001). In patients with a C-reactive protein level of more than 2 mg/l, the total number of PVC was larger than that in the other patients (p = 0.065). The patients with PVC did not show a statistically significant difference from the controls in the levels of antiviral and antibacterial antibodies. The people with PVC displayed a number of relationships between the infectious pathogen antibody titers and the ECG Holter monitoring and echocardiography readings. CONCLUSION: In the patients with PVC without signs of organic CVS pathology, the parameters of an immune response were not different from those obtained in the control group, which was likely to be associated with the involvement of the immune system in the development and maintenance of ventricular arrhythmias.

[Effect of bosentan on the clinical status and cellular immunity of patients with idiopathic pulmonary hypertension].

AIM: To study the effect of bosentan on the clinical status and cellular immunity of patients with idiopathic pulmonary hypertension (IPH). SUBJECTS AND METHODS: The study enrolled 35 patients with Functional Class (FC) II and IV IPH who had received conventional therapy for 3 months. All the patients took bosentan 125 mg/day for 4 weeks. Then they were randomized to have bosentan 125 or 250 mg/day (Groups 1 and 2). FC was assessed and 6-minute walk test (6MWT), transthoracic echocardiography (EchoCG), and right heart catheterization (RHC) were performed at baseline and after 12 weeks. Peripheral blood lymphocytes were immunophenotyped and the functional activity of neutrophils was determined by their ability to absorb latex particles at baseline and following 3 and 12 weeks. RESULTS: After 12 weeks of treatment, both groups showed a statistically significant increase in the distance covered during the 6MWT. The Borg index and FC also decreased statistically significantly. EchoCG demonstrated a statistically significant reduction in systolic pulmonary artery pressure (SPAP) in Group 1; and in Group 2, SPAP was lower at baseline and remained substantially unchanged (it statistically significantly decreased as evidenced by RHC). Bosentan statistically significantly diminished pulmonary vascular resistance in both groups. No adverse reactions were noted. At baseline, the patients showed a statistically significant elevation in NKT-like lymphocytes up to 10.79 +/- 6.2%. The other indicators of peripheral blood lymphocyte phenotyping did not exceed the normal range. The count of NKT-like lymphocytes remained significantly above the normal levels throughout the follow-up in both groups and slightly dropped in Group 1 patients only after 12 weeks of treatment. In Group 2, the level of CD3+CD25+ lymphocytes rose as compared to the normal levels at 3 and 12 weeks of treatment. At 3 weeks of treatment, there was a statistically significant difference between the groups in phagocytic number. CONCLUSION: Bosentan treatment statistically significantly improves the clinical status of patients with IPH and it is characterized by good tolerability. Bosentan does not exceed the normal count of peripheral blood NKT-like lymphocytes, but it has a direct or indirect positive effect on the B-lymphocytic component of the immune system in patients with IPH.

[Characteristics of autoimmune reactions in chronic cardiac failure of different etiology].

AIM: To characterize autoimmune reactions in patients with chronic cardiac failure (CCF) of different etiology. MATERIAL AND METHODS: Basic markers of immune activation were measured in 43 patients with coronary heart disease stage I-IIB (NYHA FC I-IV) and 44 patients with dilated cardiomyopathy (DCMP) stage I-IIB (NYHA FC I-IV). Antibodies to myocardial tissue were studied with indirect immunofluorescence. Echocardiography was made by standard recommendations with evaluation of systolic and diastolic left ventricular function. Concentrations of C-reactive protein, IgG, IgA, IgM were estimated nephelometrically. Enzyme immunoassay studied serum levels of IL-8, IL-2R, IL-6, IL-18, IL-10, IFN-gamma, endothelin. RESULTS: Patients with DCMP had higher titers of antimyocardial autoantibodies than in coronary heart disease (CHD) reflecting more severe autoimmune inflammation. In CHD endothelial, systolic and diastolic dysfunctions severity correlated with severity of inflammation. CONCLUSION: Some characteristics of autoimmune reactions in CCF determine severity of the disease course.

[Immunity in chronic bronchitis patients with significant residual changes after prior pulmonary tuberculosis].

To study the immunological features in chronic bronchitis (CB) patients with great residual changes (GRC) after prior pulmonary tuberculosis, the authors examined two groups: 1) 40 CB patients with GRC after prior pulmonary tuberculosis (a study group) and 2) 30 CB patients without a history of pulmonary tuberculosis. The examination revealed that CB patients with GRC after prior pulmonary tuberculosis were found to have higher T lymphocytes, lower B lymphocytes on an exacerbation of the disease. The phagocytic properties of neutrophils were altered as their high phagocytic activity, decreased oxygen-dependent microbicidal activity of phagocytes with their stimulation. The humoral response remained to be slightly pronounced in CB bronchitis with GRC. The low serum levels of TBC active products may suggest the low activity of lipid peroxidation processes in the study group patients. After prior pulmonary tuberculosis, antioxidative activity preserves to be high in CB patients with GRC.