Vol. 24 No. 1 (2020)
CORONARY ARTERY DISEASES

Interleukin-10 and non-classical monocytes as biomarkers of ischemic cardiomyopathy

PDF (Русский)
  • V. Shipulin,
  • S. Chumakova,
  • D. Pogonchenkova,
  • O. Urazova,
  • M. Vins,
  • A. Pryakhin,
  • V. Novickiy
V. Shipulin
Cardiology Research lnstitute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk
S. Chumakova
Siberian State Medical University, Tomsk
D. Pogonchenkova
Siberian State Medical University, Tomsk
Bio
O. Urazova
Siberian State Medical University, Tomsk; Tomsk State University of Control Systems and Radioelectronics, Tomsk
M. Vins
Siberian State Medical University, Tomsk
A. Pryakhin
Cardiology Research lnstitute, Tomsk; National Research Medical Center, Russian Academy of Sciences, Tomsk
V. Novickiy
Siberian State Medical University, Tomsk; Tomsk State University of Control Systems and Radioelectronics, Tomsk
DOI: https://doi.org/10.21688/1681-3472-2020-1-45-53

Published 2020-04-07

Keywords

  • ischemic cardiomyopathy,
  • heart failure,
  • non-classical monocytes,
  • proinflammatory cytokines

How to Cite

Shipulin, V., Chumakova, S., Pogonchenkova, D., Urazova, O., Vins, M., Pryakhin, A., & Novickiy, V. (2020). Interleukin-10 and non-classical monocytes as biomarkers of ischemic cardiomyopathy. Patologiya Krovoobrashcheniya I Kardiokhirurgiya, 24(1), 45–53. https://doi.org/10.21688/1681-3472-2020-1-45-53

Copyright (c) 2020 Shipulin V.M., Chumakova S.P., Pogonchenkova D.A., Urazova O.I., Vins M.V., Pryakhin A.S., Novickiy V.V.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Background. Chronic heart failure frequently occurs against the background of ischemic heart disease (IHD), and has also been associated with the diagnosis of ischemic cardiomyopathy (ICMP). While there are significant commonalities with respect to underlying mechanisms, it would be most important to identify differential diagnostic markers to facilitate diagnosis and verification at the early stages of disease.
Aim. The intent of this study was to perform a quantitative assessment of non-classical monocytes in patients diagnosed with IHD with or without ICMP and to identify any relationships between non-classical monocytes and plasma concentrations of proinflammatory (interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines.
Methods. We examined 44 patients diagnosed with IHD, aged 49 - 63 years, with class II-III heart failure as per the New York Heart Association criteria. Of this group, 18 were also diagnosed with ICMP. The comparison group included 14 age-matched healthy controls. Percentages of non-classical (CD14+CD16+) monocytes in peripheral blood were determined by flow cytometry and the concentrations of IL-1β, IL-4, IL-6, IL-10, IL-13 and TNF-α were measured by enzyme-linked immunosorbent assay.
Results. Amongst the patients diagnosed with ICMP, the concentration of IL-10 in blood plasma was higher than in those without this diagnosis, detected at 30.05 pg/ml (range 24.75 - 33.50 pg/ml, р=0.0412); the percentage of non-classical monocytes was lower, at 5.05% (range 4.08 - 6.58%, р=0.0094). Amongst patients diagnosed with IHD without ICMP, these parameters were within normal limits. The plasma concentrations of IL-1β, IL-6 and IL-13 in both groups were comparable to values obtained from healthy donors and IL-4 was undetectable throughout. Amongst patients diagnosed with ICMP, plasma TNF-α was detected at elevated levels that were comparable to those determined for patients diagnosed with IHD without ICMP.
Conclusion. Imbalance of cytokines in blood in patients with coronary artery disease is characterized by excess TNF-α, absence of IL-4, and normal levels of IL-1β, IL-6 and IL-13, regardless of the type of ischemic myocardial injury. In patients with ICMP, we detected an overall decrease in the fraction of non-classical monocytes in association with an increase in plasma IL-10; these features were not detected in patients diagnosed with IHD without ICMP. As such, these biological responses may be used for timely diagnosis of ICMP.

Received 27 May 2019. Revised 7 October 2019. Accepted 30 October 2019.

Funding: The work is supported by grants of the Russian Foundation for Basic Research No. 18-015-00160\19 and the President of the Russian Federation No. НШ-2690.2018.7 and No. МД-2788.2019.7.

Conflict of interest: Authors declare no conflict of interest.

Author contributions
Conception and study design: V.M. Shipulin, S.P. Chumakova
Data collection and analysis: V.M. Shipulin, S.P. Chumakova, O.I. Urazova, M.V. Vins, V.V. Novickiy
Literature review: S.P. Chumakova, D.A. Pogonchenkova, A.S. Pryakhin
Drafting the article: S.P. Chumakova, D.A. Pogonchenkova, O.I. Urazova
Critical revision of the article: V.M. Shipulin, V.V. Novickiy
Statistical analysis: S.P. Chumakova
Final approval of the version to be published: V.M. Shipulin, S.P. Chumakova, D.A. Pogonchenkova, O.I. Urazova, M.V. Vins, A.S. Pryakhin, V.V. Novickiy

PDF (Русский)

References

  1. Токмачев Р.Е., Будневский А.В., Кравченко А.Я. Роль воспаления в патогенезе хронической сердечной недостаточности. Терапевтический архив. 2016;88(9):106-110. [Tokmachev R.E., Budnevsky A.V., Kravchenko A.Ya. The role of inflammation in the pathogenesis of chronic heart failure. Therapeutic archive = Terapevticheskij archiv. 2016;88(9):106-110. (In Russ.)] https://doi.org/10.17116/terarkh2016889106-110
  2. Коваленко В.Н., Гавриш А.С. Ишемическая кардиомиопатия: нейрогуморальные и иммуновоспалительные аспекты пато- и морфогенеза. Украинский кардиологический журнал. 2013;(4):14-20. [Kovalenko V.N., Gavrish A.S. Ischemic cardiomyopathy: neurohumoral and immuno-inflammatory aspects of pato- and morphogenesis. Ukrainian cardiology journal = Ukrainskii kardiologicheskii zhurnal. 2013;(4):14-20 (In Russ.)]
  3. Казаков В.А., Суходоло И.В., Шипулин В.М., Огуркова О.Н., Гусакова А.М., Гутор С.С., Лежнев А.А., Ватолина Т.В. Поиск молекулярных маркеров послеоперационного ремоделирования левого желудочка у больных ишемической кардиомиопатией. Сибирский медицинский журнал. 2010;25(2):34-38. [Kazakov V.A., Sukhodolo I.V., Shipulin V.M., Ogurkova O.N., Gusakova A.M., Gutor S.S., Lezhnev A.A, Vatolina T.V. Search of molecular markers of postoperative remodeling of left ventricle in patients with ischemic cardiomyopathy. Siberian Medical Journal = Sibirskij medicinskij žurnal. 2010;25(2-2):34-38. (In Russ.)]
  4. Bartekova M., Radosinska J., Jelemensky M., Dhalla N.S. Role of cytokines and inflammation in heart function during health and disease. Heart Fail Rev. 2018;23(5):733-58. PMID: 29862462. https://doi.org/10.1007/s10741-018-9716-x
  5. Kaya Z., Leib C., Katus H.A. Autoantibodies in heart failure and cardiac dysfunction. Circulation Research. 2012;110(1):145-58. PMID: 22223211. https://doi.org/10.1161/CIRCRESAHA.111.243360.
  6. Shahid F., Lip G.Y., Shantsila E. Role of monocytes in heart failure and atrial fibrillation. J Am Heart Assoc. 2018;7(3). https://doi.org/10.1161/JAHA.117.007849
  7. Ziegler-Heitbrock L. The CD14+CD16+ blood monocytes: their role infection and inflammation. J Leukoc Biol. 2007;81(3):584-92. PMID: 17135573. https://doi.org/10.1189/jlb.0806510
  8. Rojas J., Salazar J., Martínez M.S., Palmar J., Bautista J., Chávez-Castillo M., Gómez A., Bermúdez V . Macrophage heterogeneity and plasticity: impact of macrophage biomarkers on atherosclerosis. Scientifica (Cairo). 2015;2015:851252. https://doi.org/10.1155/2015/851252
  9. Shapouri-Moghaddam A., Mohammadian S., Vazini H., Taghadosi M., Esmaeili S.A., Mardani F., Seifi B., Mohammadi A., Afshari J.T., Sahebkar A. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol. 2018;233(9):6425-40. PMID: 29319160. https://doi.org/10.1002/jcp.26429
  10. Чумакова С.П., Уразова О.И., Шипулин В.М., Новицкий В.В., Хардикова С.А. Цитокины как индукторы постперфузионной системной воспалительной реакции у кардиохирургических больных с различной продолжительностью коронарной патологии. Бюллетень сибирской медицины. 2017;16(4):260-269 [Chumakova S.P., Urazova O.I., Shipulin V.M., Novitsky V.V., Khardikova S.A. Cytokines as inducers of postperfusion systemic inflammatory reaction incardiosurgical patients with different duration of coronary pathology. Bulletin of Siberian Medicine. 2017;16(4):260-268. (In Russ.)] https://doi.org/10.20538/1682-0363-2017-4-260-268
  11. Закирова Н.Э., Хафизова Н.Х., Карамова И.М., Закирова А.Н, Оганов Р.Г. Иммуновоспалительные реакции при ишемической болезни сердца. Рациональная фармакотерапия в кардиологии. 2007;3(2):16-19. [Zakirova N.E., Chafizova N.H., Karamova I.M., Zakirova A.N., Oganov R.G. Immuno-inflamatory response in ischemic heart disease. Rational Pharmacotherapy in Cardiology = Racionalʹnaâ farmakoterapiâ v kardiologii. 2007;3(2):16-19. (In Russ.)] https://doi.org/10.20996/1819-6446-2007-3-2-16-19
  12. Felker G.M., Shaw L.K., O'Connor C.M., A standardized definition of ischemic cardiomyopathy for use in clinical research. J Am Coll Cardiol. 2002;39(2):210. https://doi.org/10.1016/S0735-1097(01)01738-7
  13. Лямина С.В., Малышев И.Ю. Поляризация макрофагов в современной концепции формирования иммунного ответа. Медицинские науки. Фундаментальные исследования. 2014;10:930-935. Режим доступа: http://fundamental-research.ru/ru/article/view?id=35767 [Lyamina S.V., Malyshev I.Y. Macrophage polarization in the modern concept of immune response development. Medical sciences. Fundamental research = Medicinskie nauki. Fundamentalnie issledovaniya. 2014;10:930-935. (In Russ.) Available from: http://fundamental-research.ru/ru/article/view?id=35767]
  14. Кетлинский С.А., Симбирцев А.С. Цитокины. СПб: Фолиант, 2008. 552 с. [Ketlinsky S.A., Simbirtsev A.S. Cytokines. Saint Petersburg: Folio, 2008. 552 p. (In Russ.)]
  15. Kang J.G., Sung H.J., Amar M.J., Pryor M, Remaley A.T., Allen M.D., Noguchi A.C., Springer D.A., Kwon J., Chen J., Park J.H., Wang P.Y., Hwang P.M. Low ambient oxygen prevents atherosclerosis. J Mol Med (Berl). 2016;94(3):277-86. https://doi.org/10.1007/s00109-016-1386-3
  16. Dutta P., Nahrendorf M. Monocytes in myocardial infarction. Arterioscler Thromb Vasc Biol. 2015;35(5):1066-70. PMID: 25792449, PMCID: PMC4409536. https://doi.org/10.1161/ATVBAHA.114.304652
  17. Патофизиология сердечно-сосудистой системы. Под ред. Л.С. Лилли. М.: Бином. Лаборатория знаний, 2016. 735 с. [Lilly L.S., editor. Pathophysiology of the cardiovascular system. Moscow: Binom. Knowledge Laboratory, 2016. 735 p. (In Russ.)]