MicroRNA-155 inhibition attenuates endoplasmic reticulum stress-induced cardiomyocyte apoptosis following myocardial infarction via reducing macrophage inflammation
| Autor: | Panpan Rao, Gui-Qiu Cao, Congxin Huang, Yin Zhang, Guogang Zhang, Ming-Xin Liu, Ling-Yan Zhu, Ji-Peng Zhou, Juan Hu |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Myocardial Infarction Inflammation Apoptosis Bone Marrow Cells 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Suppressor of Cytokine Signaling 1 Protein Downregulation and upregulation Fibrosis microRNA medicine Animals Antagomir Myocytes Cardiac Pharmacology Gene knockdown Chemistry Endoplasmic reticulum Macrophages NF-kappa B Antagomirs Heart medicine.disease Endoplasmic Reticulum Stress Cell Hypoxia Cell biology Rats MicroRNAs 030104 developmental biology Gene Expression Regulation medicine.symptom 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | European journal of pharmacology. 857 |
| ISSN: | 1879-0712 |
| Popis: | 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-κB (NF-κB) 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-κB pathway activation, but increased expression of SOCS1. Hypoxia increased NF-κB 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-κB pathway in cardiomyocytes. Moreover, SOCS1 knockdown in LPS-induced macrophages promoted NF-κB 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-κB pathway. |
| Databáze: | OpenAIRE |
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