Characteristics of Humoral Regulation of Differentiation of Bone Marrow Monocyte Subpopulations in Patients with Ischemic Cardiomyopathy

Abstract

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.

Keywords

• monocytopoiesis
• coronary heart disease
• cytokines