The modulatory roles of numerous circular RNAs (circRNAs) have been exposited in atherosclerosis (AS). Our study paid attention to the function of circRNA_ 0124644 (circ_0124644) in AS development, as well as its functional mechanism. The AS cell model was established by the treatment of oxidized low-density lipoprotein (ox-LDL) to human vascular endothelial cells (HUVECs). Cell proliferation and cycle were severally measured by Cell Counting Kit-8 (CCK-8) and cell cycle detection kit. The examination of apoptosis rate was executed through flow cytometry. Western blot was exploited for detecting the associated proteins. The expression levels of circ_0124644 and microRNA-149-5p (miR-149-5p) and pregnancy-associated plasma protein-A (PAPP-A) were assayed using quantitative real-time polymerase chain reaction. The combination of targets was validated via the dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull-down assay. Clonal capacity was analyzed using colony formation assay. Ox-LDL restrained HUVECs proliferation and cycle, but facilitated apoptosis. Circ_0124644 expression was increased, while miR-149-5p was downregulated in ox-LDL-treated HUVECs. Besides, circ_0124644 served as a molecular sponge of miR-149-5p and intensified the ox-LDL-induced HUVECs injury by sponging miR-149-5p. PAPP-A was a target of miR-149-5p and miR-149-5p could mitigate the HUVECs injury caused by ox-LDL through inhibiting PAPP-A. Moreover, PAPP-A was positively regulated by circ_0124644 via the miR-149-5p. In this report, we concluded the promoted role of circ_0124644 in the ox-LDL-induced endothelial injury of HUVECs via the miR-149-5p/PAPP-A axis with an emphasis on its diagnostic and therapeutic values in AS.

许多环状RNA（circRNA）的调节作用已被暴露在动脉粥样硬化（AS）中。我们的研究关注circRNA_0124644（circ_0124644）在AS发育中的功能及其功能机制。通过对人血管内皮细胞（HUVEC）氧化低密度脂蛋白（ox-LDL）的处理来建立AS细胞模型。细胞增殖和周期通过Cell Counting Kit-8（CCK-8）和细胞周期检测试剂盒分别测量。细胞凋亡率的检查通过流式细胞仪进行。利用蛋白质印迹法检测相关蛋白。使用定量实时聚合酶链反应测定circ_0124644和microRNA-149-5p（miR-149-5p）和与妊娠相关的血浆蛋白A（PAPP-A）的表达水平。通过双荧光素酶报告基因测定，RNA免疫沉淀（RIP）和RNA下拉测定法验证了靶标的组合。使用菌落形成测定法分析克隆能力。Ox-LDL抑制HUVEC的增殖和周期，但促进凋亡。在ox-LDL处理的HUVEC中，circ_0124644表达增加，而miR-149-5p被下调。此外，circ_0124644充当miR-149-5p的分子海绵，并通过使miR-149-5p海绵化而加剧了ox-LDL诱导的HUVEC损伤。PAPP-A是miR-149-5p的靶标，miR-149-5p可以通过抑制PAPP-A减轻ox-LDL引起的HUVEC损伤。而且，circ_0124644通过miR-149-5p对PAPP-A进行了正向调控。在这份报告中