Atherosclerosis (AS) is the common pathological basis of cardiovascular disease. Circular RNA circ-USP9X (hsa_-circ_0090231) has been discovered to be upregulated in oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs), but the role of circ-USP9X in ox-LDLinduced endothelial cell injury is indistinct. The purpose of the research was to investigate the role and regulatory mechanism of circ-USP9X in ox-LDL--induced endothelial cell injury. Expression of circ-USP9X was examined by quantitative real-time polymerase chain reaction. Loss-of-function experiments were performed to assess the impacts of circ-USP9X inhibition on viability, cell cycle progression, apoptosis, and tube formation, inflammation, and oxidative stress of ox-LDL-induced HUVEC. The regulatory mechanism of circ-USP9X predicted by bioinformatics analysis and verified by dual-luciferase reporter or RNA immunoprecipitation assays. We observed that circ-USP9X was upregulated in AS patients' serum and ox-LDL-induced HUVEC. Inhibition of circ-USP9X elevated viability, promoted cell cycle progression and angiopoiesis, and decreased apoptosis, inflammation, and oxidative stress of ox-LDL-induced HUVEC. Mechanically, circ-USP9X regulated chloride intracellular channel 4 (CLIC4) messenger RNA expression by sponging microRNA (miR)-599. Furthermore, miR-599 inhibitor overturned circ-USP9X silencing-mediated influence on ox-LDL-induced HUVEC injury. Also, CLIC4 overexpression reversed miR-599 elevation-mediated effect on ox-LDL-induced HUVEC injury. In conclusion, circ-USP9X silencing decreased ox-LDL-induced endothelial cell injury via the miR-599/CLIC4 axis, which offered a novel molecular mechanism to comprehend the pathology of AS.
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