PMID- 31207208 OWN - NLM STAT- MEDLINE DCOM- 20200114 LR - 20200114 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 857 DP - 2019 Aug 15 TI - MicroRNA-155 inhibition attenuates endoplasmic reticulum stress-induced cardiomyocyte apoptosis following myocardial infarction via reducing macrophage inflammation. PG - 172449 LID - S0014-2999(19)30401-7 [pii] LID - 10.1016/j.ejphar.2019.172449 [doi] AB - Endoplasmic reticulum stress (ERS)-induced cardiomyocyte apoptosis plays an important role in the pathological process following myocardial infarction (MI). Macrophages that express microRNA-155 (miR-155) mediate cardiac inflammation, fibrosis, and hypertrophy. Therefore, we investigated if miR-155 regulates ERS-induced cardiomyocyte apoptosis after MI using a mouse model, lipopolysaccharide (LPS)-induced rat bone marrow derived macrophages (BMDMs)and hypoxia-induced neonatal rat cardiomyocytes (NRCMs). In vivo, miR-155 levelswere significantly higher in the MI group compared to the sham group. MI increasedmacrophage infiltration, nuclear factor-kappaB (NF-kappaB) activation, ERS induced-apoptosis, and SOCS1 expression, all of which were attenuated by the miR-155 antagomir, with the exception of SOCS1 expression. Additionally, post-MI cardiac dysfunction was significantly improved by miR-155 inhibition. In vitro, LPS upregulated miR-155 expression in BMDMs, and the miR-155 antagomir decreased LPS-induced macrophage inflammation and NF-kappaB pathway activation, but increased expression of SOCS1. Hypoxia increased NF-kappaB pathway activation, ERS marker expression, and apoptosis in NRCMs. Interestingly, conditioned medium from LPS-induced macrophages in combination with the miR-155 antagomir decreased, while the miR-155 agomir increased, the hypoxia-induced effects in NRCM's. The miR-155 agomir effects were reversed by inhibiting the NF-kappaB pathway in cardiomyocytes. Moreover, SOCS1 knockdown in LPS-induced macrophages promoted NF-kappaB pathway activation and ERS-induced cardiomyocyte apoptosis in the hypoxia-induced NRCMs, but the SOCS1-siRNA-induced effects were markedly decreased by miR-155 antagomir treatment. These data suggest that miR-155 inhibition attenuates ERS-induced cardiomyocyte apoptosis after MI via reducing macrophage inflammation through the SOCS1/NF-kappaB pathway. 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, China. FAU - Huang, Cong-Xin AU - Huang CX AD - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei, PR China. FAU - Rao, Pan-Pan AU - Rao PP AD - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei, PR China. FAU - Cao, Gui-Qiu AU - Cao GQ AD - Department of Cardiovascular Medicine, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, PR China. FAU - Zhang, Yin AU - Zhang Y AD - Department of Cardiovascular Medicine, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, 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, China. FAU - Zhu, Ling-Yan AU - Zhu LY AD - Department of Endocrinology, The First Affiliated Hospital of NanChang University, Nanchang, 330006, China. FAU - Liu, Ming-Xin AU - Liu MX AD - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei, 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, China. Electronic address: zhangguogang@csu.edu.cn. LA - eng PT - Journal Article DEP - 20190614 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Antagomirs) RN - 0 (MIRN155 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (Mirn155 microRNA, mouse) RN - 0 (NF-kappa B) RN - 0 (Suppressor of Cytokine Signaling 1 Protein) SB - IM MH - Animals MH - Antagomirs/pharmacology MH - Apoptosis/drug effects/*genetics MH - Bone Marrow Cells/cytology MH - Cell Hypoxia/drug effects/genetics MH - Endoplasmic Reticulum Stress/drug effects/*genetics MH - Gene Expression Regulation/drug effects/genetics MH - Heart/physiopathology MH - Inflammation/genetics/pathology MH - Macrophages/cytology/drug effects/*metabolism MH - Male MH - Mice MH - MicroRNAs/*antagonists & inhibitors/genetics MH - Myocardial Infarction/genetics/immunology/pathology MH - Myocytes, Cardiac/drug effects/*pathology MH - NF-kappa B/metabolism MH - Rats MH - Signal Transduction/drug effects/genetics MH - Suppressor of Cytokine Signaling 1 Protein/genetics OTO - NOTNLM OT - Apoptosis OT - Endoplasmic reticulum stress OT - Macrophage OT - MicroRNA-155 OT - Myocardial infarction EDAT- 2019/06/18 06:00 MHDA- 2020/01/15 06:00 CRDT- 2019/06/18 06:00 PHST- 2019/03/06 00:00 [received] PHST- 2019/06/08 00:00 [revised] PHST- 2019/06/12 00:00 [accepted] PHST- 2019/06/18 06:00 [pubmed] PHST- 2020/01/15 06:00 [medline] PHST- 2019/06/18 06:00 [entrez] AID - S0014-2999(19)30401-7 [pii] AID - 10.1016/j.ejphar.2019.172449 [doi] PST - ppublish SO - Eur J Pharmacol. 2019 Aug 15;857:172449. doi: 10.1016/j.ejphar.2019.172449. Epub 2019 Jun 14.