IgE and TGF-β Signaling: From Immune to Cardiac Remodeling

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 (Fc epsilon R1) in directly promoting pathological myocardial remodeling and cardiac dysfunction. Additionally, upon blocking IgE-Fc epsilon R1 signaling using Fc epsilon R1 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-beta was the common pathway and the most pivotal mediator in IgE-Fc epsilon R1-induced cardiac remodeling and dysfunction. Furthermore, the administration of a TGF-beta inhibitor could ameliorate cardiac remodeling and improve cardiac function. Therefore, these findings suggest that IgE-Fc epsilon R1 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.

Automated summary

Cardiac remodeling is influenced by IgE and its receptor Fc epsilon R1, which directly promote pathological myocardial remodeling and dysfunction. Blocking this pathway can suppress cardiac hypertrophy and fibrosis, suggesting IgE-Fc epsilon R1 as potentially therapeutic targets for heart failure.