Prmt1 upregulated by Hdc deficiency aggravates acute myocardial infarction via NETosis
Neutrophils are mobilized and employed towards the hurt heart after myocardial infarction, and neutrophil count continues to be clinically implicated to become connected with heart disease severity. Histidine decarboxylase (HDC) continues to be implicated in controlling reactive oxidative species (ROS) and also the differentiation of myeloid cells. However, the result of HDC on neutrophils after myocardial infarction remains unclear. Here, we discovered that neutrophils were topsy-turvy employed in to the ischemic hurt part of the myocardium of Hdc deficiency (Hdc -/-) rodents. Furthermore, Hdc deficiency brought to attenuated adhesion but enhanced migration and augmented ROS/neutrophil extracellular traps (NETs) production in neutrophils. Hdc -/- mouse-derived NETs promoted cardiomyocyte dying and cardiac fibroblast proliferation/migration. In addition, protein arginine methyltransferase 1 (PRMT1) was elevated in Hdc -/- mouse-derived neutrophils but decreased with exogenous histamine treatment. Its expression might be saved by blocking histamine receptor 1 (H1R), inhibiting ATP synthesis or reducing SWItch/sucrose non fermentable (SWI/SNF) chromatin remodeling complex. Accordingly, histamine or MS023 treatment could decrease ROS and NETs ex vivo, and ameliorated cardiac function and fibrosis, combined with the reduced NETs in plasma in vivo. Together, our findings unveil the function of HDC in NETosis by histamine-H1R-ATP-SWI/SNF-PRMT1-ROS signaling and supply new biomarkers and targets for identifying and tuning the harmful immune condition in coronary disease.