The concentrations of LPO products (including those present in LDL), oxidative modification of proteins, paraoxonase activity, concentrations of antioxidants, lipid values and biomarkers of endothelial dysfunction were studied in the blood and coronary artery intima/media of male patients with coronary atherosclerosis without acute coronary syndrome. Blood levels of LDL oxidized apolipoproteins and lipoprotein (a) were higher, while the content of NO metabolites, sVCAM endothelial adhesion molecules, and LDL oxidation resistance were lower in men with mainly unstable atherosclerotic plaques in the coronary arteries in comparison with men with mainly stable plaques in the coronary arteries. Of these blood biomarkers, only NO metabolites, oxidized proteins, and sVCAM correlated with the presence of unstable atherosclerotic plaques. A significant correlation between the levels of biomarkers in the vascular wall and blood was detected only for LPO parameters.

Polymorphism of coding fragment of APOE gene was analyzed in two groups of men. The main group consisted of 77 residents of the West Siberian region aged 45-65 years with coronary atherosclerosis (documented by coronary angiography) without acute coronary syndrome with stable effort angina, functional class II-IV. The reference group consisted of 350 residents of Novosibirsk, aged 45-69 years. Statistically significant associations between genotypes of APOE gene coding part polymorphism and some key lipid risk factors (blood total and LDL cholesterol, atherogenic index, etc.) for coronary atherosclerosis were found in male residents of the West Siberian region. Elevated total mean level of cholesterol was detected in male residents of Novosibirsk with the APOE genotypes containing ε4 allele.

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.

In male patients with coronary atherosclerosis without acute coronary syndrome, the levels of inflammatory-destructive biomarkers of atherosclerotic plaque instability depended on the severity and dissemination of coronary atherosclerosis. The highest levels of C-reactive protein and matrix metalloproteinase 3 were found in men with atherosclerotic involvement of all three main coronary arteries, primarily their middle and distal segments, and in men with predominance of low-grade stenoses (<50%) of coronary arteries in areas of atherosclerotic plaques.

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Резюме. Мы предположили, что сывороточная продукция биологических маркеров, значимо отражающая степень риска развития атеросклеротического процесса и риска развития острого коронарного случая опосредована функциональным полиморфизмом комплекса генов, вовлеченных в процесс воспаления и активно влияющих на процесс взаимного регулирования продукции. Исходя из этого, нами проведен анализ частоты распределения комбинаций генотипов промоторных регионов генов цитокинов TNF-A863C; TNF-A308G; TNF-A238G; IL1B C-31T; IL1B-C511T; IL4-C590T; IL6-C174G; IL10A-1082G, IL10-А592C, регуляторных сайтов фактора роста сосудистого эндотелия VEGF-А2578С, VEGF+Т936 с сывороточным уровнем цитокинов TNFα, IL-1β, IL-6, IL-8, рецепторного антагониста IL-1 (IL-1ra), вчСРП, растворимого лиганда рецептора CD40 (sCD40L) у пациентов с атеросклерозом. Нами показано, что вклад моногенотипов в ассоциированность с уровнем продукции значительно ниже, чем отношения шансов наличия определенного уровня белковой продукции, ассоциированного со сложным генотипом.

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