Особенности воспалительного ответа моноцитов у пациентов с ранним развитием ИБС

T. V. Blokhina; T. V. Kirichenko; Yu. V. Markina; U. S. Khovantseva; S. G. Kozlov; I. S.  Melnikov; S. A.  Bazanovich

doi:10.34687/2219-8202.JAD.2024.03.0006

Authors

T. V. Blokhina Chazov National Medical Research Center of Cardiology https://orcid.org/0009-0006-1870-0314
T. V. Kirichenko Chazov National Medical Research Center of Cardiology, Moscow, Russia
Yu. V. Markina Petrovsky National Research Center of Surgery, Moscow, Russia
U. S. Khovantseva Petrovsky National Research Center of Surgery, Moscow, Russia
S. G. Kozlov Chazov National Medical Research Center of Cardiology, Moscow, Russia
I. S. Melnikov Chazov National Medical Research Center of Cardiology, Moscow, Russia
S. A. Bazanovich Chazov National Medical Research Center of Cardiology, Moscow, Russia

DOI:

https://doi.org/10.34687/2219-8202.JAD.2024.03.0006

Keywords:

premature coronary artery disease, monocytes, inflammatory cytokines, immune tolerance

Abstract

Objective. Impaired monocyte/macrophage inflammatory response is an important mechanism in the pathogenesis of atherosclerosis The aim of the study was to investigate the secretion of inflammatory cytokines by cultured monocytes/macrophages from patients with premature coronary artery disease (CAD).

Materials and methods. The study included 73 people: 38 patients with CAD, 35 patients without CAD, matched by gender and age. A primary culture of CD14+ monocytes was obtained by immunomagnetic separation. To stimulate the inflammatory response, LPS was added to the cell culture for 24 hours on days 1 and 6. Basal and LPS-stimulated secretion of the cytokines TNF-α, IL-1β, IL-6, IL-8 and MCP-1 was assessed by ELISA on days 2 and 7 of cultivation. Logistic regression analysis was performed to assess the role of the inflammatory response of monocytes along with traditional cardiovascular risk factors in the development of CAD.

Results. The levels of basal secretion of TNF-α, IL-1, IL-6, MCP-1 were higher in patients with CAD compared to participants in the control group. The level of re-stimulated secretion of TNF-α and levels of LPS-stimulated and re-stimulated secretion of IL-1 on the second and sixth days also were higher in the group with CAD. Levels of stimulated IL-6 secretion didn’t differ between the groups. Neither basal nor stimulated secretion of IL-8 differed between the CAD and control groups. LPS-stimulated MCP-1 secretion on the second day did not differ in CAD and control group. Restimulated MCP-1 secretion was higher in the CAD group. The results of logistic regression analysis showed that the secretion of IL-1β and IL-6 is independent predictor of the premature CAD, along with smoking, body mass index and serum HDL cholesterol levels.

Conclusion. Thus, the study revealed pro-inflammatory activation of monocytes/macrophages in patients with premature CAD, which consists of an increase in the basal and induced secretion of inflammatory cytokines TNF-α, IL-1β, MCP-1 and, to a lesser extent, IL-6.

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