Cao Hua, Xiao Chungang, He Zhangxiu, Huang Hong, Tang Huifang
The First Affiliated Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
The First Affiliated Hospital, Department of Nephrology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
J Inflamm Res. 2021 Oct 27;14:5523-5526. doi: 10.2147/JIR.S332591. eCollection 2021.
Cardiac remodeling is accompanied by cardiac hypertrophy, fibrosis, and dysfunction, eventually leading to heart failure (HF). However, the molecular mechanisms involved in cardiac remodeling are complicated, especially the association with immune. Immunoglobulin E (IgE) is a class of immunoglobulins involved in immune response to specific allergens. Recently, Zhao et al characterized a novel specific role of IgE and its high affinity receptor (FcεR1) in directly promoting pathological myocardial remodeling and cardiac dysfunction. Additionally, upon blocking IgE-FcεR1 signaling using FcεR1 genetic depletion or by administrating the anti-IgE monoclonal antibody omalizumab (Oma) in mice, they observed that cardiac hypertrophy and cardiac interstitial fibrosis induced by angiotensin II (Ang II) or transverse aortic constriction (TAC) were significantly suppressed. In contrast, IgE administration alone can aggravate pathological cardiac remodeling and dysfunction. RNA-seq and downstream analysis indicated that TGF-β was the common pathway and the most pivotal mediator in IgE-FcεR1-induced cardiac remodeling and dysfunction. Furthermore, the administration of a TGF-β inhibitor could ameliorate cardiac remodeling and improve cardiac function. Therefore, these findings suggest that IgE-FcεR1 maybe promising therapeutic targets for cardiac remodeling and provide an experimental basis for the use of omalizumab for HF patients combined with high serum IgE levels or allergic diseases.
心脏重塑伴随着心肌肥大、纤维化和功能障碍，最终导致心力衰竭（HF）。然而，参与心脏重塑的分子机制很复杂，尤其是与免疫的关联。免疫球蛋白E（IgE）是一类参与针对特定过敏原免疫反应的免疫球蛋白。最近，赵等人阐述了IgE及其高亲和力受体（FcεR1）在直接促进病理性心肌重塑和心脏功能障碍方面的一种新的特定作用。此外，在小鼠中使用FcεR1基因缺失或通过给予抗IgE单克隆抗体奥马珠单抗（Oma）阻断IgE-FcεR1信号传导后，他们观察到由血管紧张素II（Ang II）或主动脉缩窄（TAC）诱导的心肌肥大和心脏间质纤维化得到显著抑制。相反，单独给予IgE会加重病理性心脏重塑和功能障碍。RNA测序和下游分析表明，转化生长因子-β（TGF-β）是IgE-FcεR1诱导的心脏重塑和功能障碍的共同途径及最关键的介质。此外，给予TGF-β抑制剂可改善心脏重塑并改善心脏功能。因此，这些发现表明IgE-FcεR1可能是心脏重塑有前景的治疗靶点，并为奥马珠单抗用于血清IgE水平高或患有过敏性疾病的HF患者提供了实验依据。
