EP300 improves endothelial injury and mitochondrial dysfunction in coronary artery disease by regulating histone acetylation of SOCS1 promoter via inhibiting JAK/STAT pathway

Endothelial cell injury and mitochondrial dysfunction are crucial events during coronary artery disease (CAD). Suppressor of cytokine signaling-1 (SOCS1) is a negative mediator for inflammation, but there are few reports regarding histone acetylation of SOCS1 in CAD. The aim of the current study is to examine the impact of SOCS1 in CAD patients and human umbilical vein endothelial cells (HUVECs). We enrolled patients with CAD and healthy volunteers. HUVECs treated with ox-LDL were used as in vitro model. This study showed that SOCS1 expression was decreased in patients with CAD and ox-LDL-stimulated HUVECs. Overexpressing SOCS1 ameliorated endothelial cell injury and mitochondrial dysfunction induced by ox-LDL in vitro. Moreover, EP300 promoted SOCS1 transcription through increasing the acetylation of SOCS1 and recruiting H3K27ac to the SOCS1 gene promoter in HUVECs induced by ox-LDL. Additionally, SOCS1 repressed JAK/STAT cascade in ox-LDL-stimulated HUVECs. Silence of EP300 aggravated endothelial cell injury and mitochondrial dysfunction mediated by overexpression of SOCS1 in ox-LDL-induced HUVECs. In summary, SOCS1 alleviated endothelial injury and mitochondrial dysfunction via enhancing H3K27ac acetylation by recruiting EP300 to promoter region and inhibiting JAK/STAT pathway. These results contribute to discover underlying diagnostic biomarkers and therapeutic targets for CAD.