Inhibition of microRNA-155 attenuates sympathetic neural remodeling following myocardial infarction via reducing M1 macrophage polarization and inflammatory responses in mice
Inhibition of microRNA-155 attenuates sympathetic neural remodeling following myocardial infarction via reducing M1 macrophage polarization and inflammatory responses in mice
复制标题
抑制 microRNA-155 通过减少小鼠 M1 巨噬细胞极化和炎症反应来减弱心肌梗死后的交感神经重塑
DOI：
10.1016/j.ejphar.2019.02.001
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发表时间：
2019-05-15
影响因子：
5
通讯作者：
Zhang, Guo-Gang
中科院分区：
文献类型：
--
作者：
Hu, Juan;Huang, Cong-Xin;Zhang, Guo-Gang
Inflammation plays an important role in sympathetic neural remodeling induced by myocardial infarction (MI). MiR-155 is a vital regulator of inflammatory responses, and macrophage-secreted miR-155 promotes cardiac fibrosis and hypertrophy. However, whether miR-155 influences MI-induced sympathetic neural remodeling is not clear. Therefore, we examined the role of miR-155 in MI-induced sympathetic neural remodeling and the related mechanisms in both an mouse model and in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs). Our data showed that miR-155 expression was significantly enhanced in the myocardial tissues of MI mice compared to sham mice. Also, MI up-regulated the electrophysiological parameters, M1 macrophage polarization, inflammatory responses, and suppressor of cytokine signaling 1 (SOCS1) expression, which coincided with the increased expression of sympathetic nerve remodeling markers(nerve growth factor, tyrosine hydroxylase and growth-associated protein 43). Except for SOCS1, these proteins were attenuated by miR-155 antagomir. In vitro, LPS-stimulation promoted miR-155 expression in BMDMs. Consistent with the in vivo findings, miR-155 antagomir diminished the LPS-induced M1 macrophage polarization, nuclear factor (NF)-kappa B activation, and the expression of pro-inflammatory factors and nerve growth factor; but it increased the expression of SOCS1. Inversely, miR-155 agomir significantly potentiated LPS-induced pathophysiological effects in BMDMs. MiR-155 agomir-induced effects were reversed by the NF-kappa B inhibitor. Mechanistically, treatment with siRNA against SOCS1 augmented the aforementioned LPS-mediated activities, which were antagonized by the addition of miR-155 antagomir. In conclusion, miR-155 inhibition downregulated NGF expression via decreasing M1 macrophage polarization and inflammatory responses dependent on the SOCS1/NF-kappa B pathway, subsequently diminishing MI-induced sympathetic neural remodeling and ventricular arrhythmias (VAs).
