Ige and tgf-β signaling: From immune to cardiac remodeling

Abstract

Cardiac remodeling is accompanied by cardiac hypertrophy, fibrosis, and dys-function, 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 angioten-sin II (Ang II) or transverse aortic constriction (TAC) were significantly suppressed. In contrast, IgE administration alone can aggravate pathological cardiac remodeling and dys-function. 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.