Ischemic cardiomyopathy: blood monocytes and mediators of their differentiation
С. П. Чумакова, В. М. Шипулин, О. И. Уразова, D. A. Pogonchenkova, Maria V. Vince, Andrew S. Pryakhin, Yu. V. Kolobovnikova, Е. Г. Чурина, V. V. Novitskiy
Abstract
BACKGROUND: The three-year survival rate of patients with ischemic cardiomyopathy (ICMP) is 535 %; its pathogenesis is poorly understood. Violation of cytokine-dependent differentiation of monocytes/macrophages involved in atherogenesis may play an important role in the development of ICMP. AIMS: To characterize the disorders of monocytes subpopulation composition and mediators spectrum of blood in patients with coronary heart disease (CHD), associated with the development of ICMP. METHODS: A one-stage, clinical, controlled (case-control) study was conducted from February 2017 to December 2018. 45 patients with CHD (all men), who were in a cardiac surgery hospital, were examined before coronary bypass surgery: 19 people suffering from ICMP, and 26 people who do not suffer from ICMP, as well as 14 healthy men. In the blood of the examined individuals CD14++CD16-, CD14++CD16+, CD14+CD16++ and CD14+CD16- monocytes were determined with respect to all CD14-positive cells by flow cytometry, in blood plasma ― concentration of galectin 2 and 9, IL-4, IL-10, IFN-, M-CSF, HIF-1 by enzyme-linked immunosorbent assay (ELISA). RESULTS: The development of the ICMP accompanied by deficiency of HIF-1 and CD14+CD16++ monocytes (0.037 [0.020; 0.045] ng/ml, p = 0.019, and 5.05 [4.08; 6.58] %, p = 0.011) in combination with an excess of IL-10 (30.05 [24.75; 33.50] ng/ml, p = 0.042) in the blood. It is shown in blood of patients without ischemic cardiomyopathy the increase in the content of CD14++CD16+ cells and lack of CD14+CD16- monocytes (25.27 [15.78; 31.39] %, p = 0.038, and 2.68 [2.63; 4.09] %, p = 0.027) at normal concentration of IL-10 and HIF-1. In patients with CHD and ischemic cardiomyopathy and without ICMP in the blood the concentration of M-CSF and galectin-2 (2.00 [1.21; 3.24] pg/ml, p = 0.028, and 0.40 [0.12; 2.37] ng/ml, p = 0.004; 3.00 [1.90; 4.05] pg/ml, p = 0.003, and 3.20 [2.07; 4.00] ng/ml, p = 0.002, respectively) is reduced at normal content of galectin-9, and CD14++CD16- monocytes. IL-4 and IFN- in blood plasma are not determined (zero values). CONCLUSIONS: The development of ICMP is associated with excess of IL-10 and HIF-1 deficiency, which is accompanied by inhibition of CD14+CD16++ monocytes maturation.