title: Changes in CD4+CD25+Tregs in the pathogenesis of atherosclerosis in ApoE-/-mice.
abstract: The goal of this study was to observe the pathological characteristics of atherosclerotic plaques in the aortic walls of ApoE-/-and C57BL/6J mice and the changes of CD4+CD25+regulatory T cells (Tregs) in atherosclerotic mice. Twenty ApoE-/-mice were split into high-fat diet (AH) and normal diet (AN) groups and 10 C57BL/6J male mice were designated as the control group (BN). The serum concentrations of IL-10 and TGF-β1 were detected by enzyme-linked immunosorbent assay; paraffin sections of the aorta were stained with hematoxylin & eosin, and morphometric parameters were measured using the Image Pro Plus 6.0 system. Verhoeff stain was used to observe the distribution of elastic fibers, and immunohistochemical staining was performed to verify the phenotype of the forkhead box protein 3 (Foxp3+) CD25+cells in the atherosclerotic tissue. The proportion of CD4+CD25+Tregs in the spleen was calculated by flow cytometry. The thickness of the intima, the intima/media ratio, the plaque area, and the plaque/lumen ratio of mice in AN group were significantly larger than those of mice in BN group. The thickness of the intima, the plaque area, and the plaque/lumen ratio of the mice in AH group were significantly increased compared with those of the AN group mice. The serum concentrations of IL-10 and TGF-β1 and the percentage of splenic CD4+CD25+Tregs in AN group mice were significantly decreased compared with the control group. The serum concentrations of IL-10 and TGF-β1 and the percentage of splenic CD4+CD25+Tregs in the mice in AH group were significantly decreased compared with those in AN group. The proportions of Foxp3+and CD25+cells within the total lymphocyte population were significantly decreased in AH group mice compared with those in AN group mice. Atherosclerosis in an experimental mouse model was correlated with Treg depletion in the lymphoid tissues and plaques, indicating the important antiatherosclerotic role of CD4+CD25+Tregs. Impact statement In this article, we conclude that Tregs decreased with atherosclerosis (AS) as determined in ApoE knockout mice fed a high fat diet. It is an important matter for understanding the AS pathology.
authors.affiliation: Department of Emergency, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xue-Mei
authors.affiliation: Department of Emergency, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Jie
authors.affiliation: Department of Emergency, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Xuan
authors.affiliation: Department of Emergency, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Liao
authors.initials: L
authors.lastname: Xiao-Xing
authors.affiliation: Department of Emergency, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Chun-Lin
authors.affiliation: Department of Emergency, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu-Jie
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology*; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D006651:Histocytochemistry; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10
keywords: ApoE-KO mouse (ApoE−/− mice); Atherosclerosis; CD4+CD25+ Tregs; forkhead box protein 3