IgE Contributes to Atherosclerosis and Obesity by Affecting Macrophage Polarization, Macrophage Protein Network, and Foam Cell Formation.

Autor:	Zhang X; From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.)., Li J; From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.).; Department of Geriatrics, National Key Clinic Specialty, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China (J.L.)., Luo S; From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.)., Wang M; From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.)., Huang Q; From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.)., Deng Z; From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.)., de Febbo C; From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.)., Daoui A; From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.)., Liew PX; From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.)., Sukhova GK; From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.)., Metso J; Minerva Foundation Institute for Medical Research, National Institute for Health and Welfare, Genomics and Biobank Unit, Biomedicum 2U, Helsinki, Finland (J.M., M.J.)., Jauhiainen M; Minerva Foundation Institute for Medical Research, National Institute for Health and Welfare, Genomics and Biobank Unit, Biomedicum 2U, Helsinki, Finland (J.M., M.J.)., Shi GP; From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.)., Guo J; From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.).; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research & Key Laboratory of Emergency and Trauma of Ministry of Education, Institute of Cardiovascular Research of the First Affiliated Hospital, Hainan Medical University, Haikou 571199, China (J.G.).
Jazyk:	angličtina
Zdroj:	Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2020 Mar; Vol. 40 (3), pp. 597-610. Date of Electronic Publication: 2020 Jan 30.
DOI:	10.1161/ATVBAHA.119.313744
Abstrakt:	Objective: By binding to its high-affinity receptor FcεR1, IgE activates mast cells, macrophages, and other inflammatory and vascular cells. Recent studies support an essential role of IgE in cardiometabolic diseases. Plasma IgE level is an independent predictor of human coronary heart disease. Yet, a direct role of IgE and its mechanisms in cardiometabolic diseases remain incompletely understood. Approach and Results: Using atherosclerosis prone Apoe -/- mice and IgE-deficient Ige -/- mice, we demonstrated that IgE deficiency reduced atherosclerosis lesion burden, lesion lipid deposition, smooth muscle cell and endothelial cell contents, chemokine MCP (monocyte chemoattractant protein)-1 expression and macrophage accumulation. IgE deficiency also reduced bodyweight gain and increased glucose and insulin sensitivities with significantly reduced plasma cholesterol, triglyceride, insulin, and inflammatory cytokines and chemokines, including IL (interleukin)-6, IFN (interferon)-γ, and MCP-1. From atherosclerotic lesions and peritoneal macrophages from Apoe -/- Ige -/- mice that consumed an atherogenic diet, we detected reduced expression of M1 macrophage markers (CD68, MCP-1, TNF [tumor necrosis factor]-α, IL-6, and iNOS [inducible nitric oxide synthase]) but increased expression of M2 macrophage markers (Arg [arginase]-1 and IL-10) and macrophage-sterol-responsive-network molecules (complement C3, lipoprotein lipase, LDLR [low-density lipoprotein receptor]-related protein 1, and TFR [transferrin]) that suppress macrophage foam cell formation. These IgE activities can be reproduced in bone marrow-derived macrophages from wild-type mice, but muted in cells from FcεR1-deficient mice, or blocked by anti-IgE antibody or complement C3 deficiency. Conclusions: IgE deficiency protects mice from diet-induced atherosclerosis, obesity, glucose tolerance, and insulin resistance by regulating macrophage polarization, macrophage-sterol-responsive-network gene expression, and foam cell formation.
Databáze:	MEDLINE
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