Cytokines and HIF-1α as dysregulation factors of migration and differentiation of monocyte progenitor cells of endotheliocytes in the pathogenesis of ischemic cardiomyopathy

Background. Angiogenic endothelial dysfunction and progenitor endothelial cells (EPCs) in ischemic cardiomyopathy (ICMP) have not been studied enough.The aim. To establish the nature of changes in the cytokine profile and HIF-1α in blood and bone marrow associated with impaired differentiation of mo...

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Main Authors: O. A. Denisenko, S. P. Chumakova, O. I. Urazova, V. M. Shipulin, A. S. Pryakhin
Format: Article
Language:Russian
Published: Scientific Сentre for Family Health and Human Reproduction Problems 2022-12-01
Series:Acta Biomedica Scientifica
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Online Access:https://www.actabiomedica.ru/jour/article/view/3822
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author O. A. Denisenko
S. P. Chumakova
O. I. Urazova
V. M. Shipulin
A. S. Pryakhin
author_facet O. A. Denisenko
S. P. Chumakova
O. I. Urazova
V. M. Shipulin
A. S. Pryakhin
author_sort O. A. Denisenko
collection DOAJ
description Background. Angiogenic endothelial dysfunction and progenitor endothelial cells (EPCs) in ischemic cardiomyopathy (ICMP) have not been studied enough.The aim. To establish the nature of changes in the cytokine profile and HIF-1α in blood and bone marrow associated with impaired differentiation of monocytic progenitor cells of endotheliocytes (CD14+VEGFR2+) in the bone marrow and their migration into the blood in patients with coronary heart disease (CHD), suffering and not suffering from ICMP.Materials and methods. A single-stage, single-centre, observational case-control study was conducted involving 74 patients with CHD, suffering and not suffering from ICMP (30 and 44 people, respectively), and 25 healthy donors. In patients with CHD, bone marrow was obtained during coronary bypass surgery, peripheral blood – before surgery. Healthy donors were taken peripheral blood. The number of CD14+VEGFR2+ in bone marrow and blood was determined by flow cytometry; the concentration of IL-6, TNF-α, M-CSF, GM-CSF, MCP-1 and HIF-1α – by the method of enzyme immunoassay.Results. A high content of CD14+VEGFR2+ cells in the blood of patients with CHD without cardiomyopathy was established relative to patients with ICMP against the background of a comparable number of these cells in myeloid tissue. Regardless of the presence of ICMP in the blood, patients with CHD showed an excess of TNF-α, a normal concentration of IL-6, GM-CSF, HIF-1α and a deficiency of M-CSF, and in the bone marrow supernatant, the concentration of IL-6 and TNF-α exceeded that in the blood plasma (the level of GM-CSF – only in patients without cardiomyopathy). With ICMP, the normal concentration of MCP-1 was determined in the blood plasma, and with CHD without cardiomyopathy, its elevated content was determined.Conclusion. The formation of ICMP is accompanied by insufficient activation of EPCs migration with the CD14+VEGFR2+ phenotype in blood without disruption of their differentiation in the bone marrow, which associated with the absence of an increase in the concentration of MCP-1 in blood plasma and not associated with the plasma content of M-CSF, GM-CSF, HIF-1α, IL-6 and TNF-α.
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spelling doaj-art-fdeeefa60a734e2ab29bb393c019a9b72025-07-28T14:03:29ZrusScientific Сentre for Family Health and Human Reproduction ProblemsActa Biomedica Scientifica2541-94202587-95962022-12-0175-2213010.29413/ABS.2022-7.5-2.32433Cytokines and HIF-1α as dysregulation factors of migration and differentiation of monocyte progenitor cells of endotheliocytes in the pathogenesis of ischemic cardiomyopathyO. A. Denisenko0S. P. Chumakova1O. I. Urazova2V. M. Shipulin3A. S. Pryakhin4Siberian State Medical University; Tomsk Regional Blood CenterSiberian State Medical UniversitySiberian State Medical University; Tomsk State University of Control Systems and RadioelectronicsSiberian State Medical University; Research Institute of Cardiology, Tomsk National Research Medical Center of the Russian Academy of SciencesResearch Institute of Cardiology, Tomsk National Research Medical Center of the Russian Academy of SciencesBackground. Angiogenic endothelial dysfunction and progenitor endothelial cells (EPCs) in ischemic cardiomyopathy (ICMP) have not been studied enough.The aim. To establish the nature of changes in the cytokine profile and HIF-1α in blood and bone marrow associated with impaired differentiation of monocytic progenitor cells of endotheliocytes (CD14+VEGFR2+) in the bone marrow and their migration into the blood in patients with coronary heart disease (CHD), suffering and not suffering from ICMP.Materials and methods. A single-stage, single-centre, observational case-control study was conducted involving 74 patients with CHD, suffering and not suffering from ICMP (30 and 44 people, respectively), and 25 healthy donors. In patients with CHD, bone marrow was obtained during coronary bypass surgery, peripheral blood – before surgery. Healthy donors were taken peripheral blood. The number of CD14+VEGFR2+ in bone marrow and blood was determined by flow cytometry; the concentration of IL-6, TNF-α, M-CSF, GM-CSF, MCP-1 and HIF-1α – by the method of enzyme immunoassay.Results. A high content of CD14+VEGFR2+ cells in the blood of patients with CHD without cardiomyopathy was established relative to patients with ICMP against the background of a comparable number of these cells in myeloid tissue. Regardless of the presence of ICMP in the blood, patients with CHD showed an excess of TNF-α, a normal concentration of IL-6, GM-CSF, HIF-1α and a deficiency of M-CSF, and in the bone marrow supernatant, the concentration of IL-6 and TNF-α exceeded that in the blood plasma (the level of GM-CSF – only in patients without cardiomyopathy). With ICMP, the normal concentration of MCP-1 was determined in the blood plasma, and with CHD without cardiomyopathy, its elevated content was determined.Conclusion. The formation of ICMP is accompanied by insufficient activation of EPCs migration with the CD14+VEGFR2+ phenotype in blood without disruption of their differentiation in the bone marrow, which associated with the absence of an increase in the concentration of MCP-1 in blood plasma and not associated with the plasma content of M-CSF, GM-CSF, HIF-1α, IL-6 and TNF-α.https://www.actabiomedica.ru/jour/article/view/3822cytokinesischemic cardiomyopathycoronary heart diseaseprogenitor endothelial cellshypoxia-inducible factorbone marrow
spellingShingle O. A. Denisenko
S. P. Chumakova
O. I. Urazova
V. M. Shipulin
A. S. Pryakhin
Cytokines and HIF-1α as dysregulation factors of migration and differentiation of monocyte progenitor cells of endotheliocytes in the pathogenesis of ischemic cardiomyopathy
Acta Biomedica Scientifica
cytokines
ischemic cardiomyopathy
coronary heart disease
progenitor endothelial cells
hypoxia-inducible factor
bone marrow
title Cytokines and HIF-1α as dysregulation factors of migration and differentiation of monocyte progenitor cells of endotheliocytes in the pathogenesis of ischemic cardiomyopathy
title_full Cytokines and HIF-1α as dysregulation factors of migration and differentiation of monocyte progenitor cells of endotheliocytes in the pathogenesis of ischemic cardiomyopathy
title_fullStr Cytokines and HIF-1α as dysregulation factors of migration and differentiation of monocyte progenitor cells of endotheliocytes in the pathogenesis of ischemic cardiomyopathy
title_full_unstemmed Cytokines and HIF-1α as dysregulation factors of migration and differentiation of monocyte progenitor cells of endotheliocytes in the pathogenesis of ischemic cardiomyopathy
title_short Cytokines and HIF-1α as dysregulation factors of migration and differentiation of monocyte progenitor cells of endotheliocytes in the pathogenesis of ischemic cardiomyopathy
title_sort cytokines and hif 1α as dysregulation factors of migration and differentiation of monocyte progenitor cells of endotheliocytes in the pathogenesis of ischemic cardiomyopathy
topic cytokines
ischemic cardiomyopathy
coronary heart disease
progenitor endothelial cells
hypoxia-inducible factor
bone marrow
url https://www.actabiomedica.ru/jour/article/view/3822
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