PRMT5 knockdown enhances cell viability and suppresses cell apoptosis, oxidative stress, inflammation and endothelial dysfunction in ox-LDL-induced vascular endothelial cells via interacting with PDCD4

Atherosclerosis (AS) is an important pathological basis of cardiovascular disease (CVD). The development of AS commences with endothelial dysfunction due to vascular endothelial cell injury. It is well documented that protein arginine methyltransferase 5 (PRMT5) is highly related to cardiovascular events. BioGRID database analysis indicates that PRMT5 may interact with programmed cell death 4 (PDCD4), which is reported to be involved in AS progression. This present research was formulated to elucidate the biological roles of PRMT5/PDCD4 in vascular endothelial cell injury during AS. In this current work, HUVECs were stimulated with 100 mg/L ox-LDL for 48 h to construct an in vitro AS model. Expression levels of PRMT5 and PDCD4 were analyzed by performing RT-qPCR and western blot. The viability and apoptosis of HUVECs were determined using CCK-8, flow cytometry and western blot assays. The status of oxidative stress and inflammation was assessed via commercial detection kits and ELISA assay, respectively. Besides, biomarkers of endothelial dysfunction were detected via commercial detection kit and western blot assay. In addition, the interacting relationship between PRMT5 and PDCD4 was verified by Co-IP assay. Highly expressed PRMT5 was observed in ox-LDL-stimulated HUVECs. Knockdown of PRMT5 enhanced the viability and inhibited the apoptosis of ox-LDL-induced HUVECs as well as alleviated ox-LDL-triggered oxidative stress, inflammation and endothelial dysfunction in HUVECs. PRMT5 interacted and bound with PDCD4. Furthermore, the enhancing effect on cell viability as well as the suppressing effects on cell apoptosis, oxidative stress, inflammation and endothelial dysfunction of PRMT5 knockdown in ox-LDL-induced HUVECs were partially abolished upon up-regulation of PDCD4. To conclude, down-regulation of PRMT5 might exert protective effects against vascular endothelial cell injury during AS by suppressing PDCD4 expression.