Fat and inflammation: adipocyte-myeloid cell crosstalk in atherosclerosis

Figures

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  Figure 1. Potential role of adipocytes in atherosclerosis. (A) Healthy PVAT is mostly represented by brown adipocytes that secrete anti-inflammatory molecules, such as IL-10, Adiponectin, and Omentin. Crosstalk between adipocyte and immune cells controls adipose tissue homeostasis and vascular tone. (B) During atherosclerosis development PVAT adipocytes further differentiate toward “white” pro-inflammatory phenotype. They start to secret multiple pro-inflammatory cytokines such as IL-6, TNF, IL-1β, TGFβ, IL-23, BAFF and APRIL; chemokines, such as MCP-1 and adipokines such as Leptin and Visfatin; and downregulate anti-inflammatory adipokines such as Omentin and Adiponectin. UCP-1 expression essential for energy dissipation and thermogenesis is also downregulated. The crosstalk between adipocytes and infiltrated immune cells further promotes the recruitment of inflammatory macrophages, cDCs, pDCs and neutrophils and overall enhances inflammatory environment in PVAT. Adipocyte-derived Leptin regulates VSMC and EC, and therefore vasoconstriction and endothelial dysfunction. PVAT, Perivascular Adipose Tissue; cDC, conventional dendritic cells; pDC, plasmacytoid dendritic cells; VSMC - vascular…

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  Figure 2. Myeloid cells in aortic PVAT and atherosclerosis. (A) Healthy PVAT is composed of brown and white adipocytes and infiltrated with immune cells. Composition of myeloid cells in healthy PVAT is represented by VAM, TLF, SAM, “Crown-like” macrophages, cDCs (cDC1 and cDC2) and a small number of neutrophils. While macrophages maintain tissue homeostasis, DC can activate anti-atherogenic Treg cells, helping to maintain immune tolerance in the tissue. (B) During atherosclerosis development whitening of adipocytes and expansion of adipose tissue occurs alone with changes in the composition of myeloid cells. Pro-inflammatory, lipid associate (Trem2high and Trem2low) and metabolically activated macrophages (MMe) start to accumulate in adipose tissue and aorta, releasing pro-inflammatory chemokines and cytokines including IL-1β, TNF, IL-6, CCL2 and OPN, which in turn activate adipocytes in PVAT and provide a positive feedback loop to adipocyte whitening, inflammatory activation and subsequent pathogenic changes within PVAT. Neutrophils in adipose tissue accumulate in high numbers resulting in enhanced release of NETs and pro-inflammatory IL-1β and CXCL1. Numbers of dendritic cells, including…