Pathogenetic factors of ischaemic cardiomyopathy: results of multivariate factor analysis

Background. The pathogenesis of ischemic cardiomyopathy (ICM) is not fully understood. Aim. This study aims to identify key pathogenetic factors involved in the development of ICMP through multifactorial analysis and to determine the extent of their contribution to disease progression. Material and methods. The study included 60 patients with coronary heart disease (CHD) and ICMP, and 44 patients with CHD without evidence of cardiomyopathy.Blood and bone marrow samples were analysed by flow cytometry to assess the content of desquamated endothelial cells (DEC); classical, intermediate, non-classical, transitional monocytes; and early and late endothelial progenitor cells (EPC). In plasma and bone marrow supernatant, the concentrations of VEGF-A, SDF-1, MCP-1, M-CSF, GM-CSF, TNF-α, HIF-1α, IL-6, IL-10, IL-13, and IFN-γ were assessed using immunofluorescence and enzyme-linked immunosorbent assay. Correlation and multivariate factor analysis were performed at p < 0.05. Results. At the blood level, the primary factor terms of influence on ICMP was the concentrations of SDF-1, HIF-1α, M-CSF and DEC, accounting for 41.8% of the total variance. The second most influential factor was the concentration of IL-10 and MCP-1 (31.1%); the third was the content of late endothelial progenitor cells (EPCs) (26.3%); and the fourth, the levels of IL-6 and IL-13 (21.6%). In the bone marrow, the most significant factor was the concentrations of IL-10, IFN-γ, IL-13, M-CSF/IL-13, and classical monocytes (47.1%). The second factor involved non-classical monocytes and TNF-α (35.2%); the third, VEGF-A, MCP-1, GM-CSF, and HIF-1α (32.7%); and the fourth, early EPC and IL-6 (25.5%). In the bone marrow of patients with CHD without cardiomyopathy, a significant negative correlation was observed between IL-6 and SDF-1 concentrations (r = – 0.781, p = 0.013), while in patients with ICMP, a strong positive correlation was found between IL-6 and MCP-1 (r = 0.899, p = 0.014). Conclusions. Pathogenetic factors contributing to the development of ICMP were identified. In the blood, the most significant was an anergic mediator response of HIF-1α and SDF-1 to hypoxia with hyperproduction of IL-10. In the bone marrow, deficiency of classical monocytes and the ratio of M-CSF/IL-13 under conditions of excess IFN-γ.