Leukocyte immunoglobulin-like receptor B4 (LILRB4) negatively mediates the pathological cardiac hypertrophy by suppressing fibrosis, inflammation and apoptosis via the activation of NF-κB signaling.

Pathological cardiac hypertrophy is a leading cause of morbidity and mortality in the world. However, it is still unclear the molecular mechanism revealing the progression of the disease. In the study, we illustrated that the expression of leukocyte immunoglobulin-like receptor B4 (LILRB4), associated with the pathological development of various inflammatory diseases, was down-regulated in pressure overload-induced hearts of patients and mice. LILRB4-knockout mice developed cardiac hypertrophy and heart failure by promoting cardiac dysfunction, fibrosis, inflammation and apoptosis. Mechanistically, transforming growth factor β1 (TGF-β1) expression was significantly promoted by LILRB4 deficiency in hearts of mice after aortic banding (AB) surgery. AB-induced inflammation in cardiac tissues was accelerated by LILRB4 deletion through elevating nuclear factor κB (NF-κB) signaling pathway. Furthermore, apoptosis triggered by AB operation in heart tissues was markedly enhanced in LILRB4-KO mice through promoting Caspase-3 activation. Importantly, the in vitro study indicated that LILRB4 knockdown-promoted fibrosis; inflammation and apoptosis were largely via the NF-κB signaling. Therefore, the findings above identified LILRB4 might be a negative regulator of cardiac remodeling, illustrating that LILRB4 represented as a therapeutic target for the prevention of cardiac hypertrophy and heart failure.

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