P.P. Nesmiyanov1, M. Jain2, T.I. Rakhmatullin3, K.V. Buravleva4, E.M. Seredenina5, L.M. Samokhodskaya6
1,2,4–6 Medical Research and Educational Center of Lomonosov Moscow State University (Moscow, Russia)
2,3,5,6 Lomonosov Moscow State University (Moscow, Russia)
Erythrocytes are known to accumulate various signaling molecules contained in plasma. However, their analysis in clinical practice is limited to the determination of serum levels. The aim of this study was to determine cytokine profiles of erythrocytes in patients with coronary heart disease (CHD) and chronic heart failure (CHF). Multiplex analysis was used to determine the levels of 48 cytokines, chemokines and growth factors in erythrocyte lysate and plasma of patients with IHD / IHD + CHF, as well as in individuals without these diseases. It was found that intraerythrocytic concentrations of 17 signaling molecules significantly differed upwards from the levels in paired plasma samples (p<0.05): CTACK, eotaxin, FGF, HGF, IFN-α2, IFN-γ, IL-1β, IL -1RA, IL-8, IL-15, IL-16, IL-18, LIF, MCP-1, M-CSF, MIF, b-NGF. Among them, significant differences in patients with IHD / IHD + CHF, compared to the control group, were observed only for IFN-γ, IL-1β, IL-16, M-CSF, MIF (p<0.05) and differences with borderline significancy for MCP-1 (p=0.051). Whereas between patients with CAD and CAD + CHF, no significant differences in intraerythrocytic concentrations of signaling molecules were observed. Thus, erythrocytes appear to be a valuable source of biomarkers of inflammatory diseases and may be of interest not only in the study of ischemia-associated diseases of the cardiovascular system, but also in any other pathologies associated with systemic inflammation.
Nesmiyanov P.P., Jain M., Rakhmatullin T.I., Buravleva K.V., Seredenina E.M., Samokhodskaya L.M. Cytokine profile of red blood cells in patients with ischemic heart disease and chronic heart failure. Technologies of Living Systems. 2022. V. 19. № 4. Р. 33-41. DOI: https://doi.org/10.18127/j20700997-202204-03 (In Russian)
- Ramani T. et al. Cytokines: The Good, the Bad, and the Deadly. Int. J. Toxicol. 2015. V. 34. № 4. P. 251–268.
- Zhou X. et al. Conceptual and methodological issues relevant to cytokine and inflammatory marker measurements in clinical research. Curr. Opin. Clin. Nutr. Metab. Care. 2010. V. 13. № 5. P. 541–547.
- Kriebardis A.G. et al. RBC-derived vesicles during storage: ultrastructure, protein composition, oxidation, and signaling components. Transfusion (Paris). 2008. V. 48. № 9. P. 1943–1953.
- Weber E.W.G. et al. Perioperative blood transfusions and delayed wound healing after hip replacement surgery: effects on duration of hospitalization. Anesth. Analg. 2005. V. 100. № 5. P. 1416–1421.
- Arosa F., Pereira C., Fonseca A. Red blood cells as modulators of T cell growth and survival. Curr. Pharm. Des. 2004. V. 10. № 2.
P. 191–201. - Karsten E., Herbert B.R. The emerging role of red blood cells in cytokine signalling and modulating immune cells. Blood Rev. 2020.
V. 41. P. 100644. - Xie J. et al. Erythrocyte immune system: beyond the gas transporter. Blood & Genomics. 2022. V. 6. Iss. 1. P. 1–11.
- Theurl I. et al. On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver. Nat. Med. 2016. V. 22. № 8. P. 945–951.
- Elyasi A. et al. The role of interferon-γ in cardiovascular disease: an update. Inflamm. Res. 2020. V. 69. № 10. P. 975–988.
- Chen L.W. et al. Pitavastatin Exerts Potent Anti-Inflammatory and Immunomodulatory Effects via the Suppression of AP-1 Signal Transduction in Human T Cells. Int. J. Mol. Sci. 2019. V. 20. № 14. P. 3534.
- Severino A. et al. Atorvastatin inhibits the immediate-early response gene EGR1 and improves the functional profile of CD4+T-lymphocytes in acute coronary syndromes. Oncotarget. 2017. V. 8. № 11. P. 17529–17550.
- Taurone S. et al. Porcine coronary arteries: immunohistochemical profile of TNF-alpha, IL-1beta, TGF-beta1 and ICAM-1. Folia Morphol (Warsz). 2021.
- Rechciński T. et al. Polymorphism of Interleukin-1 Gene Cluster in Polish Patients with Acute Coronary Syndrome. J. Clin. Med. 2021.
V. 10. № 5. P. 1–14. - Ridker P.M. et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N. Engl. J. Med. 2017. V. 377. № 12.
P. 1119–1131. - Grönberg C. et al. Endarterectomy patients with elevated levels of circulating IL-16 have fewer cardiovascular events during follow-up. Cytokine. 2016. V. 85. P. 137–139.
- Krantz D. et al. IL-16 processing in sentinel node regulatory T cells is a factor in bladder cancer immunity. Scand. J. Immunol. 2020.
V. 92. № 6. P. e12926. - Sinha S.K. et al. Local M-CSF (Macrophage Colony-Stimulating Factor) Expression Regulates Macrophage Proliferation and Apoptosis in Atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2021. V. 41. № 1. P. 220–233.
- Karsten E., Hill C.J., Herbert B.R. Red blood cells: The primary reservoir of macrophage migration inhibitory factor in whole blood. Cytokine. 2018. V. 102. P. 34–40.
- Sinitski D. et al. Macrophage Migration Inhibitory Factor (MIF)-Based Therapeutic Concepts in Atherosclerosis and Inflammation. Thromb. Haemost. 2019. V. 119. № 4. P. 553–566.
- Sumaiya K. et al. Macrophage migration inhibitory factor (MIF): A multifaceted cytokine regulated by genetic and physiological strategies. Pharmacol. Ther. 2022. V. 233. P. 108024.
- Akhmetshina M.R. i dr. Zamedlenie vospaleniya i snizhenie rabotosposobnosti miokarda peptidome X, fragmentom khemokina MCP-1, u krys v modeli ishemii-reperfuzii. Tekhnologii zhivykh system. 2019. T. 16. № 2. S. 12–23. DOI: 10.18127/j20700997-201902-02
- Lin J., Kakkar V., Lu X. Impact of MCP-1 in atherosclerosis. Curr. Pharm. Des. 2014. Vol. 20. № 28. P. 4580–4588.