Ischemic cardiomyopathy: blood monocytes and mediators of their differentiation

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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.