Abstract
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.