PMID- 30721702 OWN - NLM STAT- MEDLINE DCOM- 20190722 LR - 20190722 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 851 DP - 2019 May 15 TI - Inhibition of microRNA-155 attenuates sympathetic neural remodeling following myocardial infarction via reducing M1 macrophage polarization and inflammatory responses in mice. PG - 122-132 LID - S0014-2999(19)30093-7 [pii] LID - 10.1016/j.ejphar.2019.02.001 [doi] AB - 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)-kappaB 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-kappaB 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-kappaB pathway, subsequently diminishing MI-induced sympathetic neural remodeling and ventricular arrhythmias (VAs). CI - Copyright (c) 2019. Published by Elsevier B.V. FAU - Hu, Juan AU - Hu J AD - Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Institute of Hypertension, Central South University, Changsha, Hunan, PR China. FAU - Huang, Cong-Xin AU - Huang CX AD - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China. FAU - Rao, Pan-Pan AU - Rao PP AD - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China. FAU - Zhou, Ji-Peng AU - Zhou JP AD - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Institute of Hypertension, Central South University, Changsha, Hunan, PR China. FAU - Wang, Xi AU - Wang X AD - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China. FAU - Tang, Lu AU - Tang L AD - Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Institute of Hypertension, Central South University, Changsha, Hunan, PR China. FAU - Liu, Ming-Xin AU - Liu MX AD - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China. FAU - Zhang, Guo-Gang AU - Zhang GG AD - Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Institute of Hypertension, Central South University, Changsha, Hunan, PR China. Electronic address: zhangguogang@csu.edu.cn. LA - eng PT - Journal Article DEP - 20190202 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Antagomirs) RN - 0 (MicroRNAs) RN - 0 (Mirn155 microRNA, mouse) RN - 0 (Suppressor of Cytokine Signaling 1 Protein) RN - 9061-61-4 (Nerve Growth Factor) SB - IM MH - Animals MH - Antagomirs/pharmacology MH - Gene Expression Regulation/drug effects MH - Inflammation/genetics/pathology/physiopathology MH - Macrophages/cytology/*drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*antagonists & inhibitors MH - Myocardial Infarction/genetics/metabolism/*pathology/physiopathology MH - Nerve Growth Factor/metabolism MH - Neuronal Plasticity/*drug effects MH - Suppressor of Cytokine Signaling 1 Protein/metabolism MH - Sympathetic Nervous System/drug effects/*physiopathology OTO - NOTNLM OT - Macrophage OT - MiR-155 OT - Myocardial infarction OT - Nerve growth factor OT - Sympathetic neural remodeling EDAT- 2019/02/06 06:00 MHDA- 2019/07/23 06:00 CRDT- 2019/02/06 06:00 PHST- 2018/10/23 00:00 [received] PHST- 2019/02/01 00:00 [revised] PHST- 2019/02/01 00:00 [accepted] PHST- 2019/02/06 06:00 [pubmed] PHST- 2019/07/23 06:00 [medline] PHST- 2019/02/06 06:00 [entrez] AID - S0014-2999(19)30093-7 [pii] AID - 10.1016/j.ejphar.2019.02.001 [doi] PST - ppublish SO - Eur J Pharmacol. 2019 May 15;851:122-132. doi: 10.1016/j.ejphar.2019.02.001. Epub 2019 Feb 2.