CD68 AND STABILIN-1 POSITIVE MACROPHAGES IN POSTINFARCTION MYOCARDIAL REGENERATION

Aim. Translation of experimental data on cardiac macrophages populations in postinfarction cardiac regeneration, into clinical practice.

Material and methods. In the study, 41 patients included, with fatal myocardial infarction (MI) type 1. All patients were selected to 4 groups according to fatal outcome timing. Together with routine pathohistology, immune histochemistry was done, on macrophageal infiltration. As the markers of macrophagal line we used CD68; stabilin-1 was used for M2 macrophages.

Results. The amount of CD68+ and stabilin-1+ macrophages in infarction zone increased and reached the peak in regeneratory phase, and did not decline at later stage. In peri-infarction area the amount of CD68+ macrophages increased during inflammatory phase, reached peak at reparation phase and did not change anymore either. By the results of multiple regression, the model was proposed, showing interrelations between the grade of macrophage infiltration and clinical markers of MI course.

Conclusion. Our study translates experimental results on cardiac macrophages subpopulations in postinfarction cardiac regeneration into clinical area. We observed a biphasic response of cardiac macrophages on acute ischemia, similar of that in mice. The grade stabilin-1+ macrophagal infiltration intensity increased at regeneration phase. There was significant strong positive correlation of the numbers of stabilin1+ macrophages and MI course phase, that underlies potential application of stabilin-1 as diagnostic biomarker of M2 macrophages in MI patients.

1. Snyder RJ, Lantis J, Kirsner RS, et al. Macrophages: a review of their role in wound healing and their therapeutic use. Wound Repair Regen 2016; 24: 613-29.

2. Gombozhapova A, Rogovskaya Yu, Shurupov V, et al. Macrophage activation and polarization in post-infarction cardiac remodeling. Journal of Biomedical Science 2017; 24: 13. https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-017-0322-3

3. Nahrendorf M, Swirski FK, Aikawa E, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 2007; 204: 3037-47.

4. Ryabov VV, Gombozhapova AE, Rogovskaya YV, et al. Functional plasticity of monocytes/macrophages in post-infarction cardiac regeneration and remodeling. Immunologiya 2016; 37: 305-12. (In Russ.) 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: 305-12.

5. TsujiokaH, ImanishiT, IkejimaH, etal. 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: 130-38.

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. Nahrendorf M, Swirski FK. Monocyte and macrophage heterogeneity in the heart. Circ Res 2013; 112: 1624-33.

8. Gratchev A, Sobenin I, Orekhov A, et al. Monocytes as a diagnostic marker of cardiovascular diseases. Immunobiology 2012; 217: 476-82.

9. Kzhyshkowska J. Multifunctional receptor stabilin-1 in homeostasis and disease. Scientific World Journal 2010; 10: 2039-53.

10. Gratchev A, Ovsiy I, Manousaridis I, et al. Novel monocyte biomarkers of atherogenic conditions. Curr Pharm Des 2013; 19: 5859-64.

11. Gombozhapova AE, Rogovskaya YV, Rebenkova MS, et al. Myocardial stabilin-1-positive macrophages in patients with fatal myocardial infarction. The Siberian Medical Journal 2016; 31: 100-3 (In Russ.) Гомбожапова А.Э., Роговская Ю.В., Ребенкова М.С. и др. Стабилин-1-позитивные макрофаги в миокарде пациентов с фатальным исходом инфаркта миокарда. Сибирский медицинский журнал (Томск) 2016; 31: 100-3.