PMID- 25784693
OWN - NLM
STAT- MEDLINE
DCOM- 20160210
LR  - 20220321
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 106
IP  - 3
DP  - 2015 Jun 1
TI  - IL-9 aggravates the development of atherosclerosis in ApoE-/- mice.
PG  - 453-64
LID - 10.1093/cvr/cvv110 [doi]
AB  - AIMS: 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. METHODS AND 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. CONCLUSION: 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.
CI  - Published on behalf of the European Society of Cardiology. All rights reserved. (c) 
      The Author 2015. For permissions please email: journals.permissions@oup.com.
FAU - Zhang, Wencai
AU  - Zhang W
AD  - 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.
FAU - Tang, Tingting
AU  - Tang T
AD  - 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.
FAU - Nie, Daan
AU  - Nie D
AD  - 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.
FAU - Wen, Shuang
AU  - Wen S
AD  - 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.
FAU - Jia, Chenping
AU  - Jia C
AD  - 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.
FAU - Zhu, Zhengfeng
AU  - Zhu Z
AD  - 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.
FAU - Xia, Ni
AU  - Xia N
AD  - 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.
FAU - Nie, Shaofang
AU  - Nie S
AD  - 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.
FAU - Zhou, Sufeng
AU  - Zhou S
AD  - 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.
FAU - Jiao, Jiao
AU  - Jiao J
AD  - 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.
FAU - Dong, Wenyong
AU  - Dong W
AD  - 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.
FAU - Lv, Bingjie
AU  - Lv B
AD  - 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.
FAU - Xu, Tongjie
AU  - Xu T
AD  - Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life 
      Science and Technology, Huazhong University of Science and Technology, Wuhan 
      430074, China.
FAU - Sun, Bing
AU  - Sun B
AD  - Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life 
      Science and Technology, Huazhong University of Science and Technology, Wuhan 
      430074, China.
FAU - Lu, Yuzhi
AU  - Lu Y
AD  - 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.
FAU - Li, Yuanyuan
AU  - Li Y
AD  - 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.
FAU - Cheng, Longxian
AU  - Cheng L
AD  - 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.
FAU - Liao, Yuhua
AU  - Liao Y
AD  - 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.
FAU - Cheng, Xiang
AU  - Cheng X
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150317
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Apolipoproteins E)
RN  - 0 (IL9 protein, human)
RN  - 0 (Il9r protein, mouse)
RN  - 0 (Interleukin-9)
RN  - 0 (Receptors, Interleukin-9)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
SB  - IM
CIN - Cardiovasc Res. 2015 Jun 1;106(3):348-50. PMID: 25908649
MH  - Acute Coronary Syndrome/immunology/metabolism
MH  - Animals
MH  - Antibodies, Monoclonal/administration & dosage
MH  - Aorta, Thoracic/immunology/*metabolism/pathology
MH  - Aortic Diseases/genetics/immunology/*metabolism/pathology/prevention & control
MH  - Apolipoproteins E/*deficiency/genetics
MH  - Atherosclerosis/genetics/immunology/*metabolism/pathology/prevention & control
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Endothelial Cells/immunology/metabolism
MH  - Humans
MH  - Interleukin-9/administration & dosage/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Plaque, Atherosclerotic
MH  - Receptors, Interleukin-9/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction
MH  - Vascular Cell Adhesion Molecule-1/metabolism
OTO - NOTNLM
OT  - Atherosclerosis
OT  - IL-9
OT  - Inflammation
OT  - Vascular endothelial adhesion molecule-1
EDAT- 2015/03/19 06:00
MHDA- 2016/02/11 06:00
CRDT- 2015/03/19 06:00
PHST- 2014/12/22 00:00 [received]
PHST- 2015/03/07 00:00 [accepted]
PHST- 2015/03/19 06:00 [entrez]
PHST- 2015/03/19 06:00 [pubmed]
PHST- 2016/02/11 06:00 [medline]
AID - cvv110 [pii]
AID - 10.1093/cvr/cvv110 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2015 Jun 1;106(3):453-64. doi: 10.1093/cvr/cvv110. Epub 2015 Mar 
      17.