The change in the quantity of macrophages and their stabilin-1 + M2 subpopulation in the myocardium in patients during early postinfarction period

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Investigation of the role of macrophages and their functional plasticity in reparative process accompanying myocardial infarction (MI) and postinfarction cardiac remodeling is the relevant issue of current medical science. The purpose of the study: to investigate CD68+ and stabilin-1 +-macrophage infiltration and its dynamics in patients with MI in comparison with intact myocardium. The study included patients with fatal MI type 1 (n=41). All patients were divided into 4 groups depending on the onset of death (group 1, n=13, patients who died during the first 24 hours of MI; group 2, n=11, patients who died within 24-72 hours of MI; group 3, n=9, patients who died on days 4-10; and group 4, n=8, patients who died 11-28 days after MI). The control group included patients (n=9) who died due to fatal trauma and who did not suffer from cardiovascular pathology. For evaluation of functional immunopheno-type of macrophages we used immunohistochemistry. We counted cells expressing on their surface a common macrophages marker - CD68 and specific marker of regulatory M2 macrophages that demonstrates an anti-inflammatory activity - stabilin-1 in the infarct area, peri-infarct area, and non-infarct area. In comparison with the intact myocardium (control group) the number of CD68+-macrophages in the infarct area, periinfarct area, and non-infarct area increased from the first day of disease and peaked on day 4-10. The quantity of stabilin-1 + macrophages in all zones investigated during the acute phase of MI was lower than in the intact myocardium and increased on day 4-10 in the infarct area. Furthermore, in the non-infarct zone the quantity of stabilin-1 +-macrophages was lower than its quantity in the control group both during the acute phase and the regenerative phase of MI. The data obtained indicate the participation of stabilin-1 + macrophages in process of postinfarction myocardial healing and the development of the inflammatory immune response in the myocardium during the acute phase of MI and its maintaining at late stages of the disease.

Full Text

Restricted Access

About the authors

M. S Rebenkova

Cardiology Research Institute, Tomsk National Research Medical Center of the RAS; National Research Tomsk State University

A. E Gombozhapova

Cardiology Research Institute, Tomsk National Research Medical Center of the RAS; National Research Tomsk State University

Y. V Rogovskaya

Cardiology Research Institute, Tomsk National Research Medical Center of the RAS; National Research Tomsk State University

VV. V Ryabov

Cardiology Research Institute, Tomsk National Research Medical Center of the RAS; National Research Tomsk State University; Siberian State Medical University

EG. G Churina

National Research Tomsk State University; Siberian State Medical University

J. G Kzhyshkowska

National Research Tomsk State University; Ruprecht-Karls University of Heidelberg

References

  1. Montecucco F., Carbone F., Schindler T.H. Pathophysiology of ST-segment elevation myocardial infarction: novel mechanisms and treatment. Eur. Heart J. 2016; 37: 1268-83.
  2. Rafatian N., Westcott K.V., White R.A. et al. Cardiac macrophages and apoptosis after myocardial infarction: effects of central MR blockade. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2014; 307[7]: 79-87.
  3. Рябов В.В., Гомбожапова А.Э., Роговская Ю.В. и др. Функциональная пластичность моноцитов/макрофагов в процессах восстановительной регенерации и постинфарктного ремоделирования сердца. Иммунология 2016; 37[6]: 305-12.
  4. Ismahil M.A., Hamid T., Bansal S.S. et al. Remodeling of the mononuclear phagocyte network underlies chronic inflammation and disease progression in heart failure: critical importance of the cardiosplenic axis. Circ. Res. 2014; 114[2]: 266-82.
  5. de Couto G., Liu W., Tseliou E. et al. Macrophages mediate cardio-protective cellular postconditioning in acute myocardial infarction. J. Clin. Invest. 2015; 125[8]: 3147-62.
  6. Troidl C., Mollmann H., Nef H. et al. Classically and alternatively activated macrophages contribute to tissue remodelling after myocardial infarction. J. Cell. Mol. Med. 2009; 13: 3485-96.
  7. Gombozhapova A., Rogovskaya Y., Shurupov V. et al. Macrophage activation and polarization in post-infarction cardiac remodeling. Journal of Biomedical Science 2017; 24: 13.
  8. Ben-Mordechai T., Palevski D., Glucksam-Galnoy Y. et al. Targeting macrophage subsets for infarct repair. J. Cardiovasc. Pharmacol. Ther. 2015; 20[1]: 36-51.
  9. Nahrendorf M., Swirski F.K., Aikawa E. et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J. Exp. Med. 2007; 204: 3037-47.
  10. Tsujioka H., Imanishi T., Ikejima H. et al. Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction. J. Am. Coll. Cardiol. 2009; 54: 130-8.
  11. Zajac Е., Schweighofer B., Kupriyanova T.A. et al. Angiogenic capacity of M1- and M2-polarized macrophages is determined by the levels of TiMp-1 complexed with their secreted proMMP-9. Blood 2013; 122[25]: 4054-67.
  12. Yu X., Xu M., Li N. et al. ß-elemene inhibits tumor-promoting effect of M2 macrophages in lung cancer. Biochem. Biophys. Res. Commun. 2017; 490[2]: 514-20.
  13. Chinetti-Gbaguidi G., Staels B. PPARbeta in macrophages and atherosclerosis. Biochimie 2017; 136: 59-64.
  14. Heidt T., Courties G., Dutta P. et al. Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction. Circ. Res. 2014; 115[2]: 284-95.
  15. Gratchev A., Sobenin I., Orekhov A. et al. Monocytes as a diagnostic marker of cardiovascular diseases. Immunobiology 2012; 5: 476-82.
  16. Kzhyshkowska J., Gudima A., Mogantia K. et al. Perspectives for monocyte/macrophage-based diagnostics of chronic inflammation. Transfus. Med. Hemother. 2016; 43: 66-77.
  17. Biswas S.K., Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol. 2010; 11: 889-96.
  18. Murray P.J., Allen J.E., Biswas S.K. et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014; 41: 14-20.
  19. Schönhaar K., Schledzewski K., Michel J. et al. Expression of stabilin-1 in M2 macrophages in human granulomatous disease and melanocytic lesions. International journal of clinical and experimental pathology 2014; 7[4]: 1625-34.
  20. Kzhyshkowska J., Gudima A., Moganti K. et al. Perspectives for Monocyte/Macrophage-Based Diagnostics of Chronic Inflammation. Transfus. Med. Hemother. 2016; 43: 66-77.
  21. Palani S., Elima K., Ekholm E. et al. Monocyte Stabilin-1 suppresses the activation of Th1 lymphocytes. J. Immunol. 2016; 196[1]: 115-23.
  22. Rantakari P., Patten D.A., Valtonen J. et al. Stabilin-1 expression defines a subset of macrophages that mediate tissue homeostasis and prevent fibrosis in chronic liver injury. PNAS USA 2016; 113[33]: 9298-303.
  23. Kzhyshkowska J. Multifunctional receptor stabilin-1 in homeostasis and disease. Scientific World Journal 2010; 10: 2039-53.
  24. Miller C.M., Donner A.J., Blank E.E. et al. Stabilin-1 and Stabilin-2 are specific receptors for the cellular internalization of phosphorothioate-modified antisense oligonucleotides [ASOs] in the liver. Nucleic Acids Res. 2016; 44[6]: 2782-94.
  25. Гомбожапова А.Э., Роговская Ю.В., Ребенкова М.С. и др. CD68 и стабилин-1 позитивные макрофаги в постинфарктной регенерации миокарда. Российский кардиологический журнал 2017; 11[151]: 56-61.
  26. Gombozhapova A.E., Rogovskaya Y.V., Rebenkova M.S. et al. Myocardial stabilin-1-positive macrophages in patients with fatal myocardial infarction. The Siberian Medical Journal 2016; 31:100-3.
  27. Courties G., Heidt T., Sebas M. et al. In vivo silencing of the transcription factor IRF5 reprograms the macrophage phenotype and improves infarct healing. J. Am. Coll. Cardiol. 2014; 63[15]: 1556-66.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2018 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: 

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies