In recent years, the modulatory functions of some circular RNAs (circRNAs) in the pathogenesis of atherosclerosis (AS) have been reported. Nonetheless, the role of circular RNA_0033596 (circ_0033596) in AS and its mechanism remains unclarified. In this study, oxidized low-density lipoprotein (ox-LDL) was applied to treat human umbilical vein endothelial cells (HUVECs) to establish a cell model of endothelial cell injury. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to detect the expression of circ_0033596, microRNA-217-5p (miR-217-5p), and chloride intracellular channel 4 (CLIC4) in HUVECs. The binding sites between circ_0033596 and miR-217-5p, as well as between miR-217-5p and CLIC4 mRNA 3'UTR were determined through a dual-luciferase reporter gene assay. It was found that circ_0033596 expression was increased in ox-LDL-induced HUVECs. After ox-LDL stimulation, HUVEC viability and cell cycle progression were inhibited, and the apoptosis was promoted, while circ_0033596 overexpression aggravated these effects. MiR-217-5p was identified as a downstream target of circ_0033596, and circ_0033596 negatively regulated miR-217-5p expression. CLIC4 was identified as miR-217-5p's downstream target gene and could be positively modulated by circ_0033596. All in all circ_0033596 aggravates ox-LDL-induced HUVEC apoptosis by regulating the miR-217-5p/CLIC4 axis, by which circ_0033596 participates in the pathogenesis of AS.
Keywords: Atherosclerosis; CLIC4; Circ_0033596; MiR-217-5p.