Aims To identify an imbalance of cardiac remodeling mediators and monocytes subpopulation in blood, distribution of myocardium macrophages in patients with ischemic cardiomyopathy (ICMP). Methods The study engaged 30 patients with ICMP, 26 patients with coronary heart disease (CHD) without ICMP, 15 healthy donors. Concentrations of TGFβ, MMP-9, MCP-1, galectin-3 were measured in plasma of blood from the coronary sinus and peripheral blood in CHD patients, as well as in peripheral blood in healthy donors, by enzyme immunoassay method. The ration of classical, intermediate, non-classical, transitional monocytes in peripheral blood of patients and healthy donors was assessed by flow cytometry (expression CD14, CD16); the content of CD68+ macrophages in myocardium – by immunohistochemistry method. Results In both samples of blood, the content of galectin-3 in patients with ICMP was higher than in CHD patients without ICMP and the level of TGFβ was comparable between the groups. At ICMP, the concentration of MMP-9 in sinus blood was higher than that in CHD patients without ICMP in whom an excess of MCP-1 in the general blood flow was determined. The density of distribution of CD68+ cells in the myocardium in patients with ICMP was higher in the perianeurysmal zone than in the right atrium appendage. ICMP was characterized by a deficiency of non-classical monocytes, and CHD without ICMP – by an excess of intermediate cells in peripheral blood. Conclusion Myocardium remodeling at ICMP is mediated by not so much TGFβ but intracardiac galectin-3, which determines the subpopulation composition of blood monocytes.
Background: Monocytes and macrophages play an important role in atherogenesis and myocardial remodeling. Impaired differentiation of monocyte subpopulations may contribute to ischemic cardiomyopathy (ICMP). The aim of the present research was to study the features of the humoral cytokine-dependent regulation of differentiation of classical, intermediate, non-classical and transitional monocytes in bone marrow (BM) of CHD patients with or without ICMP. Materials and Methods: Forty-five patients with coronary heart disease (CHD), with and without ICMP (19 and 26 male patients, respectively), were examined. Subpopulations of classical (CD14 ++ CD16-), intermediate (CD14 ++ CD16 +), non-classical (CD14 + CD16 +), and transitional (CD14 + CD16-) monocytes in bone marrow (BM) samples were quantified by flow cytometry. Concentrations of IL-1β, IL-13, TNF-α, IFN-γ, and M-CSF in BM supernatants and blood plasma were evaluated by ELISA. Results: Concentrations of all cytokines in the blood and IL-1β, IL-13, TNF-α, М-CSF in BM supernatants as well as the capacity of М-CSF to activate, and IL-13 to inhibit, differentiation of classical monocytes from intermediate forms-were not dependent on the clinical form of CHD. Monocytopoiesis in ICMP was characterized by elevated BM concentration of IFN-γ, low М-CSF/IL-13 ratio, and a decreased percentage of classical and intermediate monocytes, accompanied by an increased number of transitional cells in BM, as compared to patients without ICMP. Conclusion: Excess of IFN-γ and low M-CSF/IL-13 ratio in BM were associated with inhibition of differentiation of mature monocyte forms and development of ICMP.
Aim. To evaluate the ratio of the fractions of classical, intermediate, non-classical and transitional monocytes in correlation with the concentration of interleukins 4 and 6 in the blood of patients with ischemic cardiomyopathy. Methods. 18 patients with ischemic cardiomyopathy (17 men and 1 woman) aged 47-66 years with circulatory insufficiency of functional class II-III according to the classification of heart failure of the New York Heart Association, were examined. The control group included 14 healthy donors matched by gender and age to patients with ischemic cardiomyopathy without any diseases of cardiovascular system and other systems in an exacerbation stage. In blood of the patients with ischemic cardiomyopathy, the relative content of classical (CD14++CD16-), intermediate (CD14++CD16+), non-classical (CD14+CD16+) and transitional (CD14+CD16-) monocytes was assessed by flow cytometry and the concentration of interleukins 4 and 6 by enzyme-linked immunosorbent assay (ELISA). Results. It was shown that the number of non-classical monocytes in the blood of patients with ischemic cardiomyopathy was 2 times lower than normal (5.05 % [4.08; 6.58] and 10.07 % [9.34; 13.84], respectively, p < 0.01), as well as the concentration of interleukin-4 (0.02 pg/ml [0; 0.04] and 0.15 pg/ml [0.05; 0.65], respectively, p < 0.05). The number of classical monocytes in the blood of patients had a tendency to decrease, and the proportion of intermediate monocytes and the concentration of interleukin-6, on the contrary, were slightly higher than in healthy individuals, and were interdependent (r = 0.61; p < 0.05). The relative content of transitional monocytes in the blood was comparable with that of healthy donors. Conclusions. The subpopulation composition of blood monocytes in patients with ischemic cardiomyopathy is characterized by a deficiency of the fraction of non-classical monocytes with protective properties against endothelium, and interleukin-4 in the blood with a certain increase in the content of interleukin-6 and the number of intermediate cells with ability to cooperate with T-lymphocytes, which predisposes to diffuse atheromatosis of small coronary arteries and diffuse hypoxic myocardial damage in ischemic cardiomyopathy.
The aim of the investigationwas to evaluate the ratio of classical (CD14++CD16-), intermediate (CD14++CD16+), nonclassical (CD14+CD16+) and transient (CD14+CD16–) monocytes in the blood and bone marrow in patients with chronic heart failure (CHF) against ischemic cardiomyopathy (ICMP).Materials and methods. 17 patients with ICMP and 14 practically healthy donors were observed. The material of the study was venous blood (in patients and healthy donors) and red bone marrow (in patients). In the materials the relative content of different monocytes subpopulations was determined by flow cytometry. The obtained results were analyzed by statistical methods.Results. It is shown that in the blood of patients the proportion of monocytes with the phenotype CD14++CD16- is 57.77 [of 46.35; 79.76]%, CD14++CD16+ – 25.06 [4.96; 42.31]%, CD14+CD16+ 5.05 [4.08; 6.58]% and CD14+CD16- – 6.03 [3.58; 10.89]%; in the bone marrow – 43.44 [40.54; 44.68]%, 0.16 [0; 1.07]%, 0,54 [0.35; 1.07]% and 54,32 [52.83; 56.08]%, respectively, which is different from the content of the data cells subpopulations in the blood (p < 0.05). At the same time, the content of non-classical monocytes in the patients’ blood is 2 times lower than in healthy donors, and the number of other cells varies within the norm.Conclusion. The differentiation of monocytes into 4 subpopulations in patients with CHF occurs directly in the bloodstream, since mainly the classical and transitional monocyte fractions with the prevalence of the latter are present in the bone marrow. Deficiency of non-classical monocytes of blood in CHF is probably associated with a disruption of their extramedullary differentiation.
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