Dimethyl fumarate protects cardiomyocytes against oxygen-glucose deprivation/reperfusion (OGD/R)-induced inflammatory response and damages via inhibition of Egr-1.

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.