Cytokine Profile and Concentrations of Metabolic Hormones in the Blood of Overweight Men with Coronary Arteriosclerosis.

Plasma concentrations of cytokines and metabolic hormones and their association with vulnerable atherosclerotic plaques were studied in 36 overweight men (age 40-77 years; BMI 25.0-29.9 kg/m2) with coronary atherosclerosis who underwent coronary endarterectomy. According to histological analysis, the patients were divided into two groups: with stable (17 (47.2%) men) and vulnerable (19 (52.8%) men) plaques in the coronary arteries. The plasma levels of cytokines and metabolic hormones were measured by multiplex analysis: C-peptide, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1, glucagon, IL-6, insulin, leptin, monocyte chemoattractant protein-1, and TNFα. In overweight patients with vulnerable plaques, the level of glucagon was lower by 4.17 times, GIP - by 2.47 times, and insulin - by 2.1 times. At the same time, the risk of occurrence of a vulnerable plaque increases by 5.4% with a decrease in GIP concentration by 1 pg/ml irrespectively of age, as well as by 3.1% with an increase in insulin concentration by 10 pg/ml, without achieving statistical significance when included in the age model. Overweight men with coronary atherosclerosis and vulnerable plaques have lower levels of insulin, glucagon, and GIP. The levels of GIP and insulin are inversely associated with the risk of having vulnerable atherosclerotic plaque.

Adipokines and adipocytokines in men with coronary atherosclerosis and overweight.

Aim    To study concentrations of adipokines and their associations with proinflammatory cytokines in overweight men with coronary atherosclerosis. Material and methods    This study included 79 men aged 45-60 years with atherosclerosis who had undergone coronary endarterectomy during a coronary bypass surgery, and were overweight (body weight index (BWI), 25.0-29.9 kg /m2). Based on a histological analysis of plaques, the patients were divided into two subgroups: 43 men with stable atherosclerotic plaques and 36 men with unstable plaques in coronary arteries. The control group consisted of 40 age- and BWI-matched men without clinical manifestations of IHD. Blood concentrations of adipokines, including adiponectin, adipsin, lipocalin-2, resistin, and plasminogen 1 activator inhibitor were measured by a multiplex analysis with a MILLIPLEX MAP Human Adipokine Panel 1. Concentrations of proinflammatory cytokines, including tumor necrosis factor α (TNF- α), interleukin (IL)-1ß, IL-6, and C-reactive protein (CRP) were measured by enzyme immunoassay. Results    The blood concentration of lipocalin -2 was higher in patients with coronary atherosclerosis and stable or unstable atherosclerotic plaques than in the control group (p<0.01). Both subgroups of men with coronary atherosclerosis were characterized by significant differences from the control group in concentrations of TNF-α (p<0.05), CRP, and IL-6 (p<0.01). The most significant direct correlations were found between adipokines and TNF-α, IL-6, and CRP (p<0.01). Results of a logistic regression analysis showed that relative odds for the presence of significant coronary stenoses increased with increasing blood concentrations of lipocalin-2 (OR=1.005, 95 % CI: 1.002-1.008, р=0.011) and IL-6 (OR=1.582 , 95 % CI: 1.241-2.017, р=0.001).Conclusion    The changes in blood concentrations of adipokines associated with higher levels of proinflammatory cytokines may represent a factor that increases the probability of clinically significant coronary stenosis in overweight men with coronary atherosclerosis.

[The Study of Biochemical Factors of Calcification of Stable and Unstable Plaques in the Coronary Arteries of Man].

OBJECTIVE: The aim of the study was to study biochemical factors of calcification in stable and unstable plaques of coronary arteries and in the blood of patients with severe coronary atherosclerosis, to find associations of biochemical factors of calcification with the development of unstable atherosclerotic plaque. MATERIALS AND METHODS: The study included 25 men aged 60,4±6,8 years who received coronary bypass surgery. In the course of the operation intraoperative indications in men were from coronary endarteriectomy (s) artery (a - d) and histological and biochemical analyses of the samples of the intima / media. Out of 85 fragments of intima / media of coronary arteries, 15 fragments of unchanged intima / media, 39 fragments of stable atheromatous plaque and 31 fragments of unstable plaque were determined. In homogenates of samples of intima / media (after measurement of protein by the method of Lowry) and in blood by ELISA were determined by biochemical factors of calcification: osteoprotegerin, osteocalcin, an osteopontin, osteonectin, as well as inflammatory factors (cytokines, chemokines). RESULTS: A significant direct correlation (Spearman coefficient =0.607, p<0.01) between the stages of atherosclerotic focus development to unstable plaque and the degree of calcification of atherosclerotic focus development samples was found. There was an increased content of osteocalcin in stable and unstable plaques by 3.3 times in comparison with the unchanged tissue of intima / media of coronary arteries, as well as in samples with small and dust-like, with coarse-grained calcifications in comparison with samples without calcifications by 2.8 and 2.1 times, respectively. According to multivariate logistic regression analysis, the relative risk of unstable atherosclerotic plaque in the coronary artery is associated with a reduced content of osteocalcin (OR=0.988, 95 % CI 0.978-0.999, p=0.028). Also, the relative risk of calcifications in the atherosclerotic plaque in the coronary artery is associated with an increased content of osteocalcin (OR=1,008, 95 % CI 1,001-1,015, p=0,035). In men with severe coronary atherosclerosis, a significant inverse correlation was found (Spearman coefficient -0.386, p=0.022) between the content of osteoprotegerin in the vascular wall and in the blood.

Associations of Osteocalcin, Osteoprotegerin, and Calcitonin with Inflammation Biomarkers in Atherosclerotic Plaques of Coronary Arteries.

We studied associations of osteocalcin, osteoprotegerin, and calcitonin with markers of inflammation in atherosclerotic plaques in coronary arteries and assessed the influence of these biomolecules on calcification of atherosclerotic plaques. The initial stage of calcification of atherosclerotic plaques is characterized by activation of inflammatory processes, which is seen from increased levels of proinflammatory biomarkers (IL-6, IL 8, TNF-α, and IL-1ß). Progressive calcification of atherosclerotic plaques is accompanied by insignificant accumulation of calcitonin and osteoprotegerin. The exception is osteocalcin, its concentration significantly increased during calcification. The results suggest that severe vascular calcification can be regarded as non-specific marker of atherosclerosis. Instability of atherosclerotic plaques is associated with higher level of calcification.

[The incidence of respiratory symptoms and their associations with serum cotinine levels as a marker of tobacco smoking in 25-45-year-old Novosibirsk dwellers].

AIM: To study the incidence of respiratory symptoms and to reveal their associations with serum cotinine levels (SCL) in 25-45-year-old Novosibirsk dwellers. SUBJECTS AND METHODS: The WHO respiratory symptom questionnaire and the ECRHS screening questionnaire were used for a population-based survey conducted in Novosibirsk to identify respiratory symptoms; 545 people replied to the questions available in the questionnaires. SCL was determined by enzyme immunoassay on a random subsample of 182 examinees. RESULTS: The incidence of respiratory symptoms was determined among the 25-45-year-old Novosibirsk dwellers: cough (27.7%), more than 3-month cough per year (22%), sputum discharge (25%), forced respiration/wheezing in the past year (22.6%), suffocation fits in the past year (5.3%), and cough/forced respiration/stertor bouts by breathing cold air (14.9%) or contacting animals, plants, or chemical agents (16.5%). There was a significant positive correlation between SCL and the presence of cough, more than 3-month cough per year, sputum discharge, forced respiration/wheezing in the past year (compared to the examinees who did not report these symptoms). The median SCL proved to be significantly higher in the people who complained of cough, more than 3-month cough per year, sputum discharge, and forced respiration/wheezing in the past year (compared to the examinees who did not report these symptoms). The people who had a SCL of more than 3 ng/ml were ascertained to be at higher risk of cough, more than 3-month cough per year, sputum discharge, and forced respiration/wheezing in the past year than those who had a SCL of less than 3 ng/ml. CONCLUSION: The incidence of respiratory symptoms was determined among the 25-45-year-old Novosibirsk dwellers; SCL was found to be associated with the symptoms characteristic of bronchial obstructive diseases; the expediency of using the SCL threshold of 3 ng/ml as a marker of tobacco smoking was confirmed.

Relationship of blood levels of inflammatory and destructive biomarkers in coronary atherosclerosis with long-term results of surgical revascularization.

The relationships between blood levels of inflammatory and destructive biomarkers (TNF-α, IL-1ß, IL-6, IL-8, soluble CD40 ligand, high-sensitivity C-reactive protein, endothelial adhesion molecules, matrix metalloproteinase 3 and 9 and their tissue inhibitor type 1) were studied in men with coronary atherosclerosis before and 5 years after coronary artery bypass surgery. In men with unfavorable course of coronary atherosclerosis in the delayed period, the initial blood levels of C-reactive protein and TNF-α by 1.7 and 3.0 times surpassed those in patients with favorable course of the disease. Associations were revealed between elevated blood content of high-sensitivity C-reactive protein (p=0.01, odds ratio of 1.33) and IL-8 (p=0.02, odds ratio of 1.02) and deaths in the delayed period; IL-6 (p=0.01, odds ratio of 1.02) and cases of myocardial infarction; C-reactive protein (p=0.02, odds ratio of 1.24) and unfavorable course of the delayed period in general (death, myocardial infarction, worsening of angina pectoris functional class).

Activity of the inflammatory process in different types of unstable atherosclerotic plaques.

Inflammatory biomarkers and chemoattractants characteristic and important for different types (lipid; inflammatory erosive; degenerative necrotic) of unstable plaques in coronary arteries were identified and studied in male patients with coronary atherosclerosis without acute coronary syndrome we studied. Among the three types of unstable plaques, elevated concentrations of IL-1ß, IL-6, IL-8, IL-18 and monocyte chemotactic protein-1 were characteristic of not only inflammatory erosive type, but also lipid type compared with degenerative necrotic type. Thus, intensification of the inflammatory process plays an important role in the development of not only inflammatory and destructive, but also of lipid type of unstable atherosclerotic plaques.

Blood level of osteonectin in stenosing atherosclerosis and calcinosis of coronary arteries.

Blood levels of stem cell marker proteins CD34 and osteonectin were studied in male patients with coronary atherosclerosis by direct biomagnetic separation of proteins with magnetic microspheres using the PureProteome Protein A and Protein G Magnetic Beads proteomic technology. High concentration of osteonectin in the blood was detected, particularly in men with stenosing atherosclerosis and coronary artery calcinosis. Blood osteonectin concentration correlated significantly with some key biomarkers of atherosclerosis and with stenosing atherosclerosis and calcinosis of coronary arteries. The results indicate that osteonectin as a marker of stromal stem cells with osteogenic potential presumably plays an important role in atherogenesis and can serve as a new biomarker of stenosing atherosclerosis and calcinosis of coronary arteries.