Empagliflozin alleviates the development of autoimmune myocarditis via inhibiting NF-κB-dependent cardiomyocyte pyroptosis

作者：Chao Lv, Chongqing Hu, Chuanmeng Zhu, Xiaoning Wan, Chen Chen, Xinyun Ji, Yating Qin, Li Lü, Xiaomei Guo · 发表于：Biomedicine & Pharmacotherapy · 年份：2023 · DOI：10.1016/j.biopha.2023.115963 · 被引用次数：13 · 研究领域：Inflammasome and immune disorders、NF-κB Signaling Pathways、Immunodeficiency and Autoimmune Disorders

Autoimmune myocarditis, which falls within the broad spectrum of myocarditis, is characterized by an excessive inflammatory response in the heart, and can progress into dilated cardiomyopathy and irreversible heart failure in all possibility. However, effective clinical therapeutics are limited due to its complex inflammatory reactions. Empagliflozin (EMPA) has been previously demonstrated to possess anti-inflammatory properties. This study aimed to determine the improvement effects of EMPA on cardiac dysfunction under the condition of autoimmune myocarditis, and to further investigate the potential mechanisms. In vivo, all male Balb/c mice were randomly divided into four groups: control, experimental autoimmune myocarditis (EAM), EAM+EMPA and EMPA. In vitro, the effects of EMPA on IL-18-stimulated H9C2 cells were explored and the underlying molecular mechanisms were further determined. EMPA treatment significantly inhibited the development of autoimmune myocarditis, and mice treated with EMPA exhibited improved cardiac function compared with that in the EAM group, potentially through modulating pyroptosis of myocardium. Specifically, the NF-κB pathway was activated in the hearts of the EAM mice, which further activated NLRP3 inflammasome-dependent pyroptosis. EMPA treatment significantly inhibited such activation, thus alleviating inflammatory reactions in the context of EAM. Moreover, in vitro, we also observed that EMPA significantly inhibited pyroptosis of IL-18-stimulate...