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Nikita G Nikiforov, Tatiana V Kirichenko, Marina V Kubekina, Yegor S Chegodaev, Alexander D Zhuravlev, Leonid A Ilchuk, Marina A Nikolaeva, Alla S Arefieva, Mikhail A Popov, Svetlana S Verkhova, Mariam Bagheri Ekta, Alexander N Orekhov

Cytokine . 2023 Dec:172:156411. doi: 10.1016/j.cyto.2023.156411. Epub 2023 Oct 31.


Objective: Atherosclerosis is characterized by chronic inflammation in the vascular wall. Currently the violation of immune tolerance of innate immune cells is considered as a possible mechanism of chronification of inflammation. The aim of this study is to assess the inflammatory activity and tolerance of monocytes and macrophages in subclinical atherosclerosis.

Methods: A total of 55 individuals free from clinical manifestations of atherosclerosis-associated cardiovascular disease with a presence or absence of atherosclerotic plaques in the carotid arteries were included in this study. CD14+ monocytes were isolated from individuals' blood and stimulated with a single dose of lipopolysaccharide (LPS) on day 1 or with double doses of LPS on day 1 and day 6. The secretion of cytokines TNF, IL-1β, IL-6, IL-8, IL-10 and CCL2 were evaluated using ELISA.

Results: Our findings demonstrate that macrophages derived from LPS-stimulated monocytes in individuals with subclinical atherosclerosis exhibited increased secretion of IL-6, IL-10 and CCL2, which was associated with intima-media thickness, body mass index, but not with individuals' age. Moreover, macrophages from individuals with atherosclerotic plaques exhibited impaired tolerance towards the second LPS stimulation manifested by elevated secretion of the chemoattractant CCL2.

Conclusion: Increased secretion of these cytokines by macrophages may contribute to chronic local inflammation in the vascular wall by recruiting other immune cells.


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