富马酸二甲酯
心肌梗塞
药理学
氮氧化物4
细胞凋亡
促炎细胞因子
炎症
化学
活性氧
信号转导
趋化因子
医学
内科学
免疫学
生物化学
NADPH氧化酶
多发性硬化
作者
Jian Zhao,Zhaoyun Cheng,Xiaoqiang Quan,Zhouliang Xie,Leilei Zhang,Zhiwei Ding
标识
DOI:10.1016/j.intimp.2020.106733
摘要
Acute myocardial infarction (AMI) is associated with high rates of morbidity and mortality. Atherosclerosis is among the leading causes of AMI. The rupture or erosion of atherosclerotic plaques can obstruct coronary arteries, thereby leading to an acute inflammatory reaction to ischemic injury and cardiomyocyte apoptosis. Dimethyl fumarate (DMF) is a fumaric acid diester which is used for the treatment of psoriasis and multiple sclerosis. DMF is most well-known for its modulatory actions on the Nrf2 and NF-κB cellular signaling pathways. In the present study, we employed an oxygen-glucose deprivation/reoxygenation (OGD/R) model of myocardial ischemia/reperfusion injury using H9c2 cardiomyocytes to assess the potential protective effects of DMF. We found that DMF significantly improved cell viability and reduced the expression of pro-inflammatory cytokines and chemokines, including IL-6, IL-8, and MCP-1. We further demonstrated an antioxidant effect of DMF via reduced production of ROS, which was mediated through NOX4 inhibition. Tissue factor and ICAM-1 play a major role in left ventricular remodeling. DMF inhibited the expression of TF and ICAM-1 induced by OGD/R, which we demonstrated to be mediated through the Egr-1 signaling pathway, as silencing of Egr-1 suppressed the expression of TF and ICAM-1. Together, these findings demonstrate a potential role for DMF in the treatment of myocardial infarction.
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