Dysfunction of endothelial cells is now considered a vital contributor to the pathogenesis of atherosclerosis (AS). Moreover, circular RNA (circRNA) circ_0029589 has been found to be involved in the regulation of oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell damage. Nevertheless, its molecular mechanism in ox-LDL-triggered endothelial cell injury is poorly defined.
METHODS:
Human umbilical vein endothelial cells (HUVECs) treated with ox-LDL were applied as cell models of AS. Circ_0029589, microRNA-1197 (miR-1197), and Ras-related protein Rab-22A (RAB22A) expression were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, angiogenesis, and invasion were detected using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2’-deoxyuridine (EdU), flow cytometry, tube formation, and transwell assays. Western blot analysis of Cleaved-caspase-3, B-cell lymphoma-2 related X protein (Bax), and RAB22A. IL-6, IL-1β, and Tumor necrosis factor α (TNF-α) levels were gauged using ELISA kits. Superoxide Dismutase (SOD) activity and Malondiahyde (MDA) level were assessed using special kits. Bioinformatics software predicted the binding between miR-1197 and circ_0029589 or RAB22A, which was proved using dual-luciferase reporter and RNA pull-down assays.
RESULTS:
Circ_0029589 and RAB22A expression were strengthened, and miR-1197 was reduced in ox-LDL-treated HUVECs. Importantly, circ_0029589 silencing ameliorated ox-LDL-triggered HUVEC damage via promoting cell proliferation, tube formation ability, invasion, and repressing cell apoptosis, inflammation, and oxidative stress. Mechanical analysis suggested that circ_0029589 might affect RAB22A content through sponging miR-1197.
CONCLUSION:
Circ_0090231 might protect against ox-LDL-mediated HUVEC injury via the miR-1197/RAB22A axis, which provides a therapeutic strategy for endothelial cell damage of AS.
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