title: Probucol Protects Against Atherosclerosis Through Lipid-lowering and Suppressing Immune Maturation of CD11c+ Dendritic Cells in STZ-induced Diabetic LDLR-/- Mice.
abstract: Probucol, an agent characterized by lipid-lowering and antioxidant property, retards atherosclerosis effectively. To test the hypothesis that probucol might act its antiatherosclerotic role by suppressing immune maturation of dendritic cells (DCs), 7-week-old LDLR mice were rendered diabetic with streptozotocin (STZ) and then fed either a high-fat diet only or added with 0.5% (wt/wt) probucol for 4 months, and human monocyte-derived dendritic cells were preincubated with or without probucol and stimulated by oxidized low-density lipoprotein. In STZ-induced diabetic LDLR mice, probucol treatment significantly lowered plasma total cholesterol and high-density lipoprotein-cholesterol levels; regressed aortic atherosclerotic lesions; reduced splenic CD40, CD80, CD86, MHC-II expression, and plasma IL-12p70 production; and decreased the expression of CD11c DCs within atherosclerotic lesions. In vitro, oxidized low-density lipoprotein promoted human monocyte-derived dendritic cells maturation; stimulated CD40, CD86, CD1a, HLA-DR expression; increased tumor necrosis factor-α production; and decreased IL-4 production. However, these effects were obviously inhibited by probucol pretreatment. In conclusion, our study indicated that probucol effectively retarded atherosclerosis at least partly through lipid-lowering and inhibiting immune maturation of CD11c DCs in STZ-induced diabetic LDLR mice.
authors.affiliation: *Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; †Department of cardiology, Huashan Hospital, Fudan University, Shanghai, China; ‡Institute of Biomedical Science, Fudan University, Shanghai, China; and §Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Xueting
authors.initials: X
authors.lastname: Jin
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dong
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: George
authors.initials: G
authors.lastname: Liu
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Keqiang
authors.initials: K
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D039521:CD11c Antigen / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood*; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D003925:Diabetic Angiopathies / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D059305:Diet, High-Fat; D015536:Down-Regulation; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D011341:Probucol / Q000494:pharmacology*; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D013311:Streptozocin
chemical_list: D015415:Biomarkers; D039521:CD11c Antigen; D016207:Cytokines; D000960:Hypolipidemic Agents; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein; D013311:Streptozocin; D002784:Cholesterol; D011341:Probucol