The role of immunoglobulin E and mast cells in hypertension
The role of immunoglobulin E and mast cells in hypertension
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免疫球蛋白E和肥大细胞在高血压中的作用
DOI：
10.1093/cvr/cvac010
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发表时间：
2022-02-02
影响因子：
10.8
通讯作者：
Wang, Jing
中科院分区：
文献类型：
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作者：
Ge, Weipeng;Guo, Xiaoxiao;Wang, Jing
高血压是心血管疾病和全球死亡率的主要原因。免疫球蛋白E（IgE）在过敏性疾病中起关键作用，其通过其受体（Fc受体1）参与血管和心脏重塑的发病机制。本研究旨在揭示IgE和Fc受体1在高血压中的作用。方法和结果在此，我们报道了IgE水平显着增加，在高血压患者以及在高血压小鼠血管紧张素II（Ang II）诱导。Ang II诱导的血管重塑和高血压在Fc ε R1基因敲除小鼠或抗IgE单克隆抗体治疗的小鼠中显著减轻。类似地，用奥马珠单抗（一种临床IgE拮抗剂）治疗也显著抑制Ang II诱导的高血压。此外，在肥大细胞（MC）、平滑肌细胞（SMC）或内皮细胞（EC）中，在Fc ε R1条件性敲除的小鼠中评价了IgE-Fc ε R1在高血压中的细胞贡献。我们的数据显示，IgE介导的高血压在很大程度上依赖于MC中的Fc β R1，而不是SMC和EC。最后，小鼠骨髓来源的MCs的RNA-seq和信号通路分析表明，白细胞介素6（IL-6）是IgE介导的高血压的关键介质之一。IgE刺激MCs产生的IL-6促进活性氧的产生，降低内皮细胞中磷酸化内皮一氧化氮合酶的水平，导致内皮功能障碍。结论IgE参与了高血压的发病过程，其机制可能部分是通过激活MCs的IgE-Fc受体1信号通路而实现的。因此，IgE可能代表IgE介导的高血压的新的治疗靶点。
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 (Fc epsilon R1). In this study, we aimed to reveal the role of IgE and Fc epsilon R1 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 Fc epsilon R1 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-Fc epsilon R1 in hypertension was evaluated in mice with Fc epsilon R1 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 Fc epsilon R1 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-Fc epsilon R1 signalling in MCs. Thus, IgE may represent a new therapeutic target for IgE-mediated hypertension.