The peripheral blood monocytes of atherosclerotic patients are pre-activated and have some of the features of tissue macrophages. Their adhesion to the endothelium is 1.5 times higher than that of monocytes from healthy subjects, and they express a number of receptors and antigens typical of tissue macrophages. Additionally, earlier we showed that the biosynthesis of gangliosides, whose main function is the formation of membrane rafts, is significantly activated in blood monocytes from atherosclerotic patients, as well as during the in vitro differentiation of normal monocytes into macrophages. In this study, we investigated the expression of membrane rafts on various monocyte subsets from healthy subjects and atherosclerotic patients. Based on flow cytometry results, the monocytes in the examined atherosclerotic patients were found to differ from those in healthy subjects by a twofold increase in the proportion of the intermediate subset (CD14(++)/CD16(+)) and by enhancement in the expression of the fractalkine receptor CX3CR1 on the intermediate and non-classical subsets (CD14(++)/CD16(+) and CD14(+)/CD16(++)) (2.3 and 1.8 times, respectively). This suggests a pre-activated state of monocytes in atherosclerotic patients. At the same time, the expression of the membrane raft marker on the monocyte subsets was similar in both studied groups. However, a study of the in vitro differentiation of monocytes into macrophages showed that the membrane raft expression increased 2 times as early as on the 1st day of culturing and 3 times on the 7th day compared to that in freshly isolated monocytes. Therefore, it is suggested that monocytes in atherosclerosis accumulate gangliosides that are used to form membrane rafts during the macrophage differentiation after the migration of monocytes into the arterial intima.
Моноциты периферической крови больных атеросклерозом предактивированы и обладают некоторыми чертами тканевых макрофагов. Их адгезия к эндотелию в 1.5 раза выше, чем у моноцитов здоровых субъектов, и они экспрессируют ряд рецепторов и антигенов, характерных для тканевых макрофагов. В дополнение к этому ранее мы показали, что в моноцитах крови больных атеросклерозом, так же как и при in vitro-дифференцировке моноцитов в макрофаги, значительно активируется биосинтез ганглиозидов, главная функция которых - формирование мембранных рафтов. В настоящей работе мы исследовали экспрессию мембранных рафтов на различных субпопуляциях моноцитов в норме и при атеросклерозе. Моноциты больных атеросклерозом, как показано методом проточной цитометрии, отличались от моноцитов здоровых субъектов двукратным увеличением процентного содержания промежуточной субпопуляции (CD14 ++ /CD16 + ) и повышением экспрессии фракталкинового рецептора CX3CR1 на промежуточной и неклассической субпопуляциях (CD14 ++ /CD16 + и CD14 + /CD16 ++ ) (в 2.3 и 1.8 раза соответственно). Это свидетельствует о предактивированном состоянии моноцитов больных. В то же время экспрессия маркера мембранных рафтов была одинаковой на субпопуляциях моноцитов обеих исследованных групп. Однако изучение in vitro дифференцировки моноцитов в макрофаги показало, что уже на первые сутки культивирования экспрессия мембранных рафтов повышалась в 2 раза и к 7-му дню возрастала в 3 раза в сравнении со свежевыделенными моноцитами. Таким образом, можно предположить, что при атеросклерозе моноциты накапливают ганглиозиды, которые используются для формирования мембранных рафтов при макрофагальной дифференцировке моноцитов после их миграции в интиму артерий.
Aim. To determine the association between cardiovascular disease risk factors and presence of coronary arteries lesions with the involvement of left main coronary artery (LMCA). Methods. We included male and female patients 40-60 years old, who underwent coronary angiography: with coronary atherosclerosis and LMCA involvement — group 1 (n—83), with coronary atherosclerosis without any lesions in LMCA — group 2 (n—88), and patients with intact coronary arteries — group 3 (n—34). All patients identified Cardiovascular disease traditional risk factors as well as lipoprotein (a), interleukin-6, C-reactive protein serum levels were determined in all patients. Results. A percent of women was higher in group 3 compare to group 1 and group 2 (59% vs 17% p—0.00001 and 59% vs 16% p—0.00001, respectively), as well as a percent of smokers was lower (19% vs 44% p—0.03 and 19% vs 61% p—0.0001, respectively), as was expected. All patients were treated with hypolipidemic therapy, however the levels of high density lipoprotein was significantly lower in the group 1 compare to group 2 and group 3 (1.04+0.29 vs 1.2+0.49, p—0.04 and 1.04+0.29 vs 1.28+0.35, p—0.005, respectively). The levels of lipoprotein (a) were not significantly different between the groups. Serum interleukin-6 had a tendency to increase in the group 1 versus group 3 (4.31+5.24 vs 2.06+1.8, p—0.06, respectively).
Aim: To determine the influence of the secretory phospholipase A2 group IIA (sPLA2-IIA) on the severity of coronary atherosclerosis. Methods: We studied patients (n = 271), who underwent coronary angiography. They were divided into 3 groups by the number of affected coronary arteries and the control group. Risk factors for cardiovascular disease, the level and activity of sPLA2-IIA and С-reactiveprotein (CRP) were determined. Results: The level of sPLA2 -IIA increased with increasing number of affected arteries (p = 0,03). Activity of sPLA2 has tendency to increase with increasing number of affected arteries (p = 0,07). The high density lipoprotein decreased with increasing degree of coronary atherosclerosis (p = 0,0008), and the level ofleukocytes increased (p = 0,03). CRP level was not significantly different between the groups, but correlated with the concentration of sPIA2-IIA (r= 0,32). Conclusion: The increase of the severity of coronary atherosclerosis is associated with a significant increase of the level of sPLA2 -IIA.
It is well known that inflammation plays an important role in the etiology and pathogenesis of atherosclerosis. At the present time one of the inflammatory markers secretory phospholipase A2 (secPIA2) is actively investigated. The published data indicate that a high level of secPLA2 group IIA (secPLA2-HA) is a predictor of cardiovascular events in patients with acute coronary syndrome and stable coronary artery disease. In addition to the concentration of secPIA2-IlA the activity of secPLA2 is also a predictor of adverse cardiovascular events s. However published studies “ are contradictory and therefore in this review the clinical trials results systematization has done.
Determination of association between risk factors for cardiovascular disease (CVD) and the lesions of coronary arteries with involving the left main coronary artery (LMCA). We studied male and female aged 40-60 years who performed coronary angiography: with stenosis of the coronary arteries including LMCA group 1(n = 83), without lesions of the LMCA – group 2 (n = 88), and patients with intact coronary arteries group 3 (n = 34). All patients identified traditional risk factors for CVD, and levels of Lp(a), IL-6, CRP. In the group 3 the number of women were significantly higher versus to groups 1 and 2 (59% vs 17% p=0.00001 and 59% vs 16% p=0.00001, respectively), as well as the number of smokers significantly lower in the same group (19% vs 44% p=0.03 and 19% vs 61% p=0.0001, respectively), as was expected. All patients were treated with hypolipidemic therapy, however the levels of HDL-C was significantly lower in the group 1 versus to groups 2 and 3 (1.04 ±0.29 vs 1.2 ±0.49, p=0.04 and 1.04 ±0.29 vs 1.28 ±0.35, p=0.005, respectively). The level of Lp(a) was not significantly different between the groups. Serum IL-6 had a tendency to increase in the group 1 versus to group 3 (4.31 ±5.24 vs 2.06 ±1.8, p = 0.06, respectively). We determined a lower levels of HDL-C and tendency to increase the level of IL-6 in patients with lesions of the LMCA compared with other groups.