Leukocyte Ig-like receptor B4 (Lilrb4a) alleviates cardiac dysfunction and isoproterenol-induced arrhythmogenic remodeling associated with cardiac fibrosis and inflammation

Abstract

BackgroundHeart failure (HF) is usually accompanied by the activation of the sympathetic nerve, and the excessive activation of the sympathetic nerve also promotes cardiac remodeling and cardiac dysfunction. In the isoproterenol (ISO) induced animal model, it is often accompanied by myocardial hypertrophy, fibrosis, and inflammation. Leukocyte immunoglobulin-like receptor B4a (Lilrb4a) is an immunosuppressive regulatory receptor and plays a vital role in cardiovascular disease. However, the effect of Lilrb4a on ventricular arrhythmias from ISO-induced mice model remains unclear. ObjectiveThe purpose of this study was to explore the role and molecular mechanism of Lilrb4a in ISO-induced arrhythmogenic remodeling. MethodsLilrb4a knockout mice and Lilrb4a overexpression mice were infused with ISO (15 mg/kg/24h, 4 weeks). Echocardiography and Histology were used to evaluate myocardial hypertrophy and cardiac structural remodeling. Surface ECG and Electrophysiological examination were used to evaluate cardiac electrical remodeling and the susceptibility to ventricular arrhythmias (VAs). qRT-PCR and Western Blotting were used to detect the expression levels of ion channel proteins and signal pathway proteins. ResultsThe results discovered that ISO induced cardiac hypertrophy, fibrosis, and inflammation, and led to electrical remodeling and the occurrence of VAs. Lilrb4a alleviated cardiac structural and electrical remodeling and protected against the occurrence of VAs in ISO-induced mice by gain- or loss-of-function approaches. The mechanism is that Lilrb4a inhibited NF-kB signaling and p38 signaling activation medicated by TAK1. ConclusionsLilrb4a alleviates cardiac dysfunction and isoproterenol-induced arrhythmogenic remodeling associated with cardiac fibrosis and inflammation through the regulation of NF-kB signaling and p38 signaling activation.