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Abstract：
Background Abnormal regulation of vascular smooth muscle cells is regarded as the iconic pathological change of aortic dissection (AD). Herein, we aim to identify circ_0022920 as a crucial regulator in AD. Methods and Results Microarray analysis of circular RNAs, messenger RNAs, and micro RNAs in patients with AD was performed, and we identified that circ_0022920 was significantly downregulated in these patients. The Pearson correlation analysis uncovered the negative correlation between miR-650 and circ_0022920 or TGFβR1 (transforming growth factor beta receptor 1). Angiotensin II was used to treat human aortic vascular smooth muscle cells (HASMCs) and mice as models for AD. Hematoxylin and eosin and Masson\'s trichrome staining were used to analyze AD histopathology. Cell proliferation was analyzed with Cell Counting Kit-8 assay and EdU incorporation. Cell migration was assessed with transwell and wound healing assays. Enhanced circ_0022920 expression dramatically inhibited HASMC proliferation and migration and maintained contractile marker expression induced by angiotensin II, whereas miR-650 exerted opposite effects. MiR-650 was a target of circ_0022920. MiR-650 targeted IRF1 (interferon regulatory factor 1) and thus negatively regulated TGFβR1 expression to promote HASMC proliferation and migration and inhibit contractile marker expression. Circ_0022920 suppressed the progression of AD in vivo. Conclusions Circ_0022920 modulates the contractile phenotype of HASMCs via regulating the miR-650-IRF1-TGFβR1 axis in angiotensin II-induced models for AD, which provides potential therapeutic targets for AD.
摘要：
背景血管平滑肌细胞异常调节是主动脉夹层(AD)的标志性病理改变。在这里，我们的目标是将circ_0022920确定为AD的关键调节因子。方法和结果环状RNA的微阵列分析，信使RNA，并对AD患者进行了微小RNA，我们发现circ_0022920在这些患者中显著下调。Pearson相关分析揭示了miR-650与circ_0022920或TGFβR1(转化生长因子β受体1)之间的负相关。血管紧张素II用于治疗人主动脉血管平滑肌细胞(HASMC)和小鼠作为AD的模型。采用苏木精、伊红和Masson三色染色对AD进行组织病理学分析。用细胞计数试剂盒-8测定和EdU掺入分析细胞增殖。用transwell和伤口愈合试验评估细胞迁移。增强的circ_0022920表达显著抑制HASMC增殖和迁移，并维持血管紧张素II诱导的收缩标志物表达，而miR-650发挥相反的作用。MiR-650是circ_0022920的靶标。MiR-650靶向IRF1（干扰素调节因子1），从而负向调节TGFβR1的表达以促进HASMC增殖和迁移并抑制收缩标记表达。Circ_0022920在体内抑制AD的进展。结论Circ_0022920通过调节miR-650-IRF1-TGFβR1轴在血管紧张素II诱导的AD模型中调节HASMCs的收缩表型,这为AD提供了潜在的治疗靶标。
