Lipid metabolism in experimental autoimmune atherosclerosis

Abstract

Introduction. The current paradigm regarding the pathogenesis of atherosclerosis is that there is a causal relationship between dyslipidemia and the formation of atherosclerotic plaque. In studies of the last few decades, convincing data have been obtained regarding the involvement of autoimmune reactions to lipoproteins in the pathogenesis of atherosclerosis. However, the relationship between the autoimmune reaction to lipoproteins, lipid metabolism, and atherosclerotic lesions remains unclear.

The aim of the study was to examine lipid metabolism in rats and rabbits with atherosclerosis-like aortic changes induced by immunization with native human high-density lipoproteins (nhHDL).

Material and methods. We compared the lipid profile of blood plasma and peripheral blood mononuclear cells (PBMC) in nhHDL/IFA-immunized, incomplete Freund’s adjuvant (IFA) injected, and intact rats and rabbits, as well as the production of inflammatory and proatherogenic cytokines TNFα and PDGF-BB by periaortic adipocytes in rabbits.

Results. Changes in the lipid profile of blood plasma and PBMC in animals immunized with nhHDL/IFA and in IFA-injected animals were similar, while atherosclerosis-like changes in the aortic wall were observed only in the nhHDL/IFA-immunized animals. Consequently, the changes in lipid metabolism of rabbits and rats immunized with nhHDL/IFA were induced by the IFA and these changes were not associated with atherosclerotic aortic lesions. Production of TNFα and PDGF-BB by periaortic adipocytes in rabbits that were immunized with nhHDL/IFA and developed atherosclerosis was the same as that of intact rabbits.

Conclusion. We found no evidence that changes in lipid metabolism are necessary for the development of atherosclerotic aortic lesions induced by the immune response to HDL.

Keywords:atherosclerosis animal model; antibodies to HDL; lipid metabolism; incomplete Freund’s adjuvant

For citation: Menshikov I.V., Zerjawi A.K.A., Beduleva L.V., Fomina K.V., Terentiev A.S., Abisheva N.N., Cherepanov I.S. Lipid metabolism in experimental autoimmune atherosclerosis. Immunologiya. 2022; 43 (5): 593–605. DOI: https://doi.org/10.33029/0206-4952-2022-43-5-593-605 (in Russian)

Funding. The work was supported by the Ministry of Science and High Education of the Russian Federation (project number 0827-2020-0012).

Conflict of interests. The authors declare no conflict of interests.

Authors’ contribution. Conceptualization, writing (review and editing) – Menshikov I.V.; investigation, writing – Zerjawi A.K.A.; methodology, writing – Beduleva L.V.; investigation, writing – Fomina K.V.; investigation – Terentiev A.S., Abisheva N.N., Cherepanov I.S.

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