• Wencai Zhang, Tingting Tang, Daan Nie, Shuang Wen, Chenping Jia, Zhengfeng Zhu, Ni Xia, Shaofang Nie, Sufeng Zhou, Jiao Jiao, Wenyong Dong, Bingjie Lv, Tongjie Xu, Bing Sun, Yuzhi Lu, Yuanyuan Li, Longxian Cheng, Yuhua Liao, and Xiang Cheng.
• 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.
• Cardiovasc. Res. 2015 Jun 1; 106 (3): 453-64.

AimsRecently, 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 ResultsIL-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.ConclusionOur 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.Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

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