LAUSR

ABSTRACT Atherosclerosis (AS) is a common cardiovascular disease with high morbidity and mortality. The pathogenesis of AS is closely related to endothelial dysfunction, which is mainly induced by oxidative stress, inflammation, and enhanced adhesion of monocytes to endothelial cells on the vessel wall. Febuxostat is a novel anti-gout agent recently reported to exert protective effects on endothelial dysfunction. The present study aims to investigate the protective capacity of Febuxostat against ox-LDL-induced injury and monocyte attachment to endothelial cells. Human aortic valve endothelial cells (HAVECs) were stimulated with ox-LDL in the presence or absence of Febuxostat (5, 10 μM) for 6 hours. Mitochondrial ROS were measured using MitoSox red staining and the level of protein carbonyl was detected using ELISA. The expressions of IL-6, TNF-α, tissue factor (TF), VCAM-1, and ICAM-1 were evaluated with qRT-PCR and ELISA assays. Calcein-AM staining was utilized to determine the attachment of U937 monocytes to HAVECs. qRT-PCR and Western blot were used to measure the expression level of early growth response 1 (Egr-1) in HAVECs. Firstly, the elevated expression of LOX-1, activated oxidative stress, excessive secreted inflammatory factors, and promoted expression of TF induced by stimulation with ox-LDL were significantly reversed by Febuxostat, indicating a protective effect of Febuxostat against endothelial dysfunction. Secondly, the upregulated VCAM-1 and ICAM-1, as well as the increased proportion of adhered monocytes to HAVECs induced by ox-LDL were significantly alleviated by Febuxostat. Lastly, the promoted expression level of Egr-1 induced by ox-LDL was pronouncedly suppressed by Febuxostat. We conclude that Febuxostat protected HAVECs from ox-LDL-induced injury and monocytes attachment.