title: Regulatory T cells prevent angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E knockout mice.
abstract: To test the hypothesis that adoptive transfer of regulatory T cells (Tregs) may dose-dependently inhibit the formation of angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E knockout mice, we established an animal model of abdominal aortic aneurysm by angiotensin II infusion in apolipoprotein E knockout mice. Then mice received different treatment with PBS, low-dose Tregs, high-dose Tregs, or CD25-depleting PC61 antibody. Histopathologic analysis showed that the incidence of abdominal aortic aneurysm was 80%, 76%, 27%, and 71% in the PBS, low-dose Tregs, high-dose Tregs, and PC61 groups, respectively. Tregs treatment markedly decreased macrophage and CD4+ T-cell infiltration and preserved the medial smooth muscle cells. Furthermore, Tregs decreased the levels of proinflammatory cytokines, matrix metalloproteinase-2 (MMP-2) and MMP-9, increased the expression of anti-inflammatory interleukin-10 and transforming growth factor-β, and suppressed apoptosis and oxidative stress. In vitro, Tregs inhibited the response of human aortic smooth muscle cells to angiotensin II and reduced the expression of proinflammatory cytokines, MMP-2 and MMP-9, possibly by inhibiting the activation of nuclear factor-κB and extracellular signal-regulate kinase 1/2. In addition, Tregs downregulated macrophage type 1-related genes and upregulated macrophage type 2-related genes. However, Tregs-mediated effects were largely reversed by disrupting cell-cell contact or using neutralizing antibodies against interleukin-10 and transforming growth factor-β. Adoptive transfer of Tregs dose-dependently prevents angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E knockout mice. The mechanisms may involve declined proinflammatory cytokine expression and MMP-2 and MMP-9 levels and enhanced anti-inflammatory cytokine expression, which is mediated by direct cell-cell contact and soluble mediators.
authors.affiliation: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Meng
authors.affiliation: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Yang
authors.affiliation: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Guipeng
authors.initials: G
authors.lastname: An
authors.affiliation: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Kong
authors.affiliation: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Jiang
authors.affiliation: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China zhangcheng8003@126.com zhangyun@sdu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China zhangcheng8003@126.com zhangyun@sdu.edu.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D019264:Adoptive Transfer; D000804:Angiotensin II; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation*
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D000804:Angiotensin II; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: T-lymphocytes, regulatory; aortic aneurysm, abdominal; inflammation; macrophages