title: IL-9 aggravates the development of atherosclerosis in ApoE-/- mice.
abstract: OBJECTIVE
  Recently, interleukin (IL)-9 was found to be involved in the pathogenesis of many inflammatory diseases. Here, we tested whether IL-9 was related to atherosclerosis and investigated the underlying mechanisms.
  
  
  RESULTS
  IL-9R was expressed in mouse aortic endothelial cells (MAECs) and aortic tissues, and IL-9 levels were elevated in plasma and aortic arches in Apolipoprotein E-deficient (ApoE-/-) mice. ApoE-/- mice fed a western diet for 10 weeks were administered recombinant mouse IL-9 (rIL-9) or anti-IL-9 neutralizing monoclonal antibody (mAb). Mice treated with rIL-9 developed markedly larger plaques in both the aorta and aortic root. Immunohistochemical studies demonstrated increases in both vascular endothelial adhesion molecule-1 (VCAM-1) expression and the infiltration of inflammatory cells, including T cells and macrophages, in plaques. However, treatment with the anti-IL-9 mAb caused the opposite effect. The administration of rIL-9 did not affect the splenic T cell or peripheral monocyte subsets. Meanwhile, IL-9 induced VCAM-1 expression in MAECs mainly via a STAT3-dependent pathway, consequently increasing monocyte-endothelial adhesion. Moreover, treatment with anti-VCAM-1 mAb partially abrogated the IL-9-induced increase in plaque area. In addition, CD4(+)IL-9(+) T cells and IL-9 were increased in patients with acute coronary syndrome, and the levels of IL-9 in culture supernatants and soluble VCAM-1 (sVCAM-1) in plasma were significantly positively correlated in the enrolled patients.
  
  
  CONCLUSIONS
  Our results demonstrated that IL-9 exerted pro-atherosclerotic effects in ApoE-/- mice at least partially by inducing VCAM-1 expression, which mediated inflammatory cell infiltration into atherosclerotic lesions.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Wencai
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Tang
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Daan
authors.initials: D
authors.lastname: Nie
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wen
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Chenping
authors.initials: C
authors.lastname: Jia
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Zhengfeng
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Xia
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Shaofang
authors.initials: S
authors.lastname: Nie
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Sufeng
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Wenyong
authors.initials: W
authors.lastname: Dong
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Bingjie
authors.initials: B
authors.lastname: Lv
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Tongjie
authors.initials: T
authors.lastname: Xu
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Longxian
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China nathancx@mail.hust.edu.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
mesh_terms: D054058:Acute Coronary Syndrome / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001013:Aorta, Thoracic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016906:Interleukin-9 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic; D053651:Receptors, Interleukin-9 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; C508607:IL9 protein, human; C508448:Il9r protein, mouse; D016906:Interleukin-9; D053651:Receptors, Interleukin-9; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D019010:Vascular Cell Adhesion Molecule-1
keywords: Atherosclerosis; IL-9; Inflammation; Vascular endothelial adhesion molecule-1