Sinomenine protects against oxidized low-density lipoprotein-induced human umbilical vein endothelial cell injury through regulating the myocyte enhancer factor 2 A/C-X-C motif chemokine ligand 14 pathway.

Atherosclerosis (AS) is a chronic vascular disease characterized by inflammatory response and lipid deposition in the arterial walls caused by endothelial injury. Sinomenine (SIN) could delay AS progression by attenuating endothelial inflammation. However, its role and mechanism in the oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVEC) injury remain unclear. An in vitro model of AS in HUVECs was established using ox-LDL. CCK-8 detected cell viability. ROS, SOD, MDA, TNF-α, IL-β, and IL-6 were evaluated using commercial kits. Western blot was used to detect NLRP3, apoptosis-associated speck-like protein containing ASC, activated caspase-1, GSDMD-N, Arg1, CD206, iNOS, CXCL14, and MEF2A protein levels. CXCL14 mRNA level was measured using RT-qPCR. Binding between MEF2A and CXCL14 promoter was validated using dual-luciferase reporter and ChIP. SIN exposure alleviated ox-LDL-caused oxidative stress, inflammation, pyroptosis, and M1 macrophage polarization in HUVECs. CXCL14 or MEF2A silencing abolished the protective effect of SIN on ox-LDL-caused HUVEC injury. Mechanistically, MEF2A directly interacts with CXCL14 promoter and promotes its transcription. SIN treatment restrained ox-LDL-evoked HUVEC injury and M1 macrophage polarization partly via targeting the MEF2A/CXCL14 axis, providing new insights for future research on the application of SIN in AS treatment.