The role of immunoglobulin E and mast cells in hypertension

Author:

Ge Weipeng1,Guo Xiaoxiao2ORCID,Song Xiaomin1,Pang Junling1ORCID,Zou Xuan1,Liu Yonglin3ORCID,Niu Yongliang3,Li Zhengqing3,Zhao Hongmei1,Gao Ran1,Wang Jing1ORCID

Affiliation:

1. Department of Pathophysiology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College , Dongdansantiao 5, Dongcheng District, Beijing 100730 , China

2. Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing , China

3. Shenmu Hospital, The Affiliated Shenmu Hospital of Northwest University , Shaanxi Province, Shenmu 719300 , China

Abstract

Abstract Aims Hypertension is the major cause of cardiovascular diseases and global mortality. Immunoglobulin E (IgE), which plays crucial roles in allergic diseases, has been implicated in the pathogenesis of vascular and cardiac remodelling via its receptor (FcεR1). In this study, we aimed to reveal the role of IgE and FcεR1 in hypertension. Methods and results Herein, we reported that IgE levels were significantly increased in hypertensive patients as well as in hypertensive mice induced by angiotensin II (Ang II). Ang II-induced vascular remodelling and hypertension were significantly alleviated in FcεR1 genetic knockout mice or in mice treated with anti-IgE monoclonal antibody. Similarly, treatment with omalizumab (a clinical IgE antagonist) also markedly inhibited Ang II-induced hypertension. Furthermore, the cellular contribution of IgE–FcεR1 in hypertension was evaluated in mice with FcεR1 conditional knockout in mast cell (MC), smooth muscle cell (SMC), or endothelial cell (EC). Our data revealed that IgE-mediated hypertension is largely dependent on FcεR1 in MCs but not SMCs and ECs. Finally, RNA-seq and signalling pathway analyses of mouse bone marrow-derived MCs suggested that interleukin 6 (IL-6) is one of critical mediators in IgE-mediated hypertension. IL-6 derived from IgE-stimulated MCs promoted reactive oxygen species production and decreased the levels of phosphorylated endothelial nitric oxide synthase in ECs, leading to endothelial dysfunction. Conclusion Our findings reveal that IgE contributes to the pathogenesis of hypertension, at least partially through activating the IgE–FcεR1 signalling in MCs. Thus, IgE may represent a new therapeutic target for IgE-mediated hypertension.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

Reference41 articles.

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