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The Cytokine Profile of Myocardial Cells with Coronary Heart Disease and Ischemic Cardiomyopathy

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Abstract

In this work, a comparative analysis of the myocardial cytokine profile was carried out in patients with coronary heart disease (CHD) and in patients with ischemic cardiomyopathy (ICM) against the background of CHD. The concentrations of 41 cytokines secreted by a 24-h tissue culture of the myocardium, intraoperatively collected from the right atrial (RA) appendage (control) and a peri-infarct zone (PZ) of the left ventricle (LV), were determined by the flow fluorimetry method using a multiplex test system. The aim of the work was to study in vitro the cytokine profile of myocardial cells to search for possible predictors of unfavorable outcomes of the surgical treatment of patients with CHD and ICM. The myocardial secretion of the pro-inflammatory molecules GM-CSF and IFN-γ increased significantly in patients with ICM against the background of CHD (up to 78–80 pg/g, p < 0.05) as compared with zero values in the case of CHD. At the same time, a threefold decrease in the concentration of the Fractalkine 3 ligand (Flt-3L, fms-like tyrosine kinase 3 ligand) was observed. A decrease in the secretion of Flt-3L was noted namely in the PZ–LV as compare with the RA appendage. In addition, the concentrations of fibroblast growth factor-2 (FGF-2), platelet-derived growth factor AB/BB (PDGF-AB/BB), interleukins IL-15 and IL-4, as well as regulated upon activation, normal T cell expressed and secreted (RANTES/CCL5), sharply decreased in the tissue myocardial PZ–LV culture as compared with RA appendage. The detected changes are analyzed using correlation and regression analyses; possible predictors of the risk of surgical treatment of patients from two groups are suggested. Pro-inflammatory cytokines (IL-5, IL-6) and chemokines (Flt-3L, IL-8), as well as factors of angiogenesis (VEGF) and angiostasis (IP-10), are suggested to be considered as potential markers of unfavorable outcome of the surgical treatment of cardiovascular diseases.

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ACKNOWLEDGMENTS

The authors are grateful to Siberian State Medical University for partial support within the “Priority 2030 Strategic Academic Leadership Program.”

Funding

This work was supported by the Russian Foundation for Basic Research, project no. 20-315-90051, “Molecular, Cellular, and Tissue Markers of Unfavorable Outcomes of the Surgical Treatment of Patients with Ischemic Cardiomyopathy.”

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Authors and Affiliations

  1. Department of Morphology and General Pathology, Siberian State Medical University, 634050, Tomsk, Russia

    A. I. Stelmashenko & I. A. Khlusov

  2. Laboratory of Cellular and Microfluidic Technologies, Siberian State Medical University, 634050, Tomsk, Russia

    A. I. Stelmashenko, L. S. Litvinova & I. A. Khlusov

  3. Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012, Tomsk, Russia

    S. L. Andreev & V. M. Shipulin

  4. Center for Immunology and Cell Biotechnologies, Immanuel Kant Baltic Federal University, 236041, Kaliningrad, Russia

    L. S. Litvinova, V. V. Malashchenko, N. M. Todosenko & N. D. Gazatova

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  1. A. I. Stelmashenko
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Contributions

A.I. Stelmashenko: setting aim and objectives, planning the experiments, analyzing the results, writing the article; I.A. Khlusov: setting aims and objectives, planning the experiments, writing the article; S.L. Andreev, V.M. Shipulin: provision of clinical material; A.I. Stelmashenko, L.S. Litvinova, V.V. Malashchenko, N.D. Todosenko, N.M. Gazatova: setting up the experiments.

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Correspondence to L. S. Litvinova.

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ETHICS APPROVAL AND CONSENT TO PARTICIPATE

All studies were conducted in accordance with the principles of biomedical ethics as outlined in the 1964 Declaration of Helsinki and its later amendments. They were also approved by the Ethics Committee of Siberian State Medical University, Tomsk, Russia, protocol No. 7981 dated December 16, 2019. Each participant in the study provided a voluntary written informed consent after receiving an explanation of the potential risks and benefits, as well as the nature of the upcoming study.

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Translated by A. Barkhash

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Abbreviations: CHD—coronary heart disease; ICM—ischemic cardiomyopathy; ELIS—enzyme-linked immunosorbent; ESI—end-systolic index; LV—left ventricle; PZ—peri-infarct zone; RA—right atrium; CXCL/CCL—C-X-C chemokine motif/C-C ligand motif; EGF—epidermal growth factor; FGF-2—basic fibroblast growth factor; Flt-3L—fractalkine-3 ligand; Fractalkine—fractalkine; G-CSF—granulocyte colony-stimulating factor; GM-CSF—granulocyte-monocyte colony-stimulating factor; GRO—growth-related oncogene; IFN—interferon; IL—interleukin; IP-10—interferon γ-inducible protein 10; MCP—monocyte chemotactic protein; MDC—macrophage-derived chemokine; MIP—macrophage inflammatory protein; PDGF—platelet-derived growth factor; RANTES/CCL5—regulated upon activation, normal T-cell expressed and secreted; sCD40L—type I transmembrane glycoprotein; TGF-α—transforming growth factor α; TNF—tumor necrosis factor; VEGF—vascular endothelial growth factor.

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Stelmashenko, A.I., Andreev, S.L., Litvinova, L.S. et al. The Cytokine Profile of Myocardial Cells with Coronary Heart Disease and Ischemic Cardiomyopathy. Cell Tiss. Biol. 18, 45–57 (2024). https://doi.org/10.1134/S1990519X24010097

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