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. 2022 Apr 22;7:131. doi: 10.1038/s41392-022-00955-7

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Key cells involved in atherosclerosis. a Phenotypic switching of VSMCs in atherosclerosis. In the healthy arterial wall, VSMCs are a contractile phenotype expressing contractile proteins (ACTA2, SM22α, Myocardin (MYOCD), and MYH11). Upon PDGF-BB and TNF-α, VSMCs switch to a synthetic phenotype, which increases the production of ECM, exosomes, pro-inflammatory cytokines, and MMPs. VSMCs release calcifying vesicles to propagate vascular calcification. KLF4 promotes phenotypic switching of VSMCs into foam-like, macrophage-like, osteochondrocyte-like, adipocyte-like, and Sca1⁺ mesenchymal-like VSMCs. Shear stress induces transdifferentiation of VSMCs into endothelial-like cells. The transcription factors TCF21 and OCT4 (octamer binding transcription factor) promote modulation of VSMCs into atheroprotective myofibroblast-like phenotype. b Plasticity and function of macrophages in atherosclerosis. Monocytes differentiate toward various phenotypes of macrophages in response to stimuli in atherosclerotic lesions. Among them, M1 macrophages secret pro-inflammatory cytokines; M2, M (Hb), and Mhem phenotypes are anti-inflammatory; Mox macrophages exhibit an antioxidant effect; and M4 phenotypes express pro-inflammatory cytokines and have impaired phagocytosis. c Lymphocytes in atherosclerosis. CD4⁺ T cells can differentiate into distinct lineages including T helper 1 (Th1), Th2, Th17, T regulatory (Treg), and many other Th cells. Th1 cells produce TNF-α and IFN-γ, indicating a pro-inflammatory and pro-atherogenic role of Th1 cells. Treg cells promote inflammatory resolution and dampen atherosclerosis progression via the production of IL-10 and TGFβ. The effect of Th2, Th9, and Th17 cells on the development of atherosclerosis remains controversial. B cells can exert both a pathogenic and protective role in atherosclerosis. B cells have two main subsets B1 and B2 cells. B1 cells exert an atheroprotective effect by the release of IgM antibodies against oxidation-specific epitopes. Similarly, Breg cells also act atheroprotective by the production of IL-10. B2 cells exhibit both pro-atherogenic and atheroprotective depending on the inflammatory microenvironment