Department of Vascular Surgery, Xiangya Hospital, Central South University, 86 Xiangya Road, Changsha, Hunan Province 410008, China.
Department of Vascular Surgery, Xiangya Hospital, Central South University, 86 Xiangya Road, Changsha, Hunan Province 410008, China.
Eur J Pharmacol. 2019 Jun 15;853:145-152. doi: 10.1016/j.ejphar.2019.03.030. Epub 2019 Mar 19.
As the most common form of aortic aneurysm, abdominal aortic aneurysm (AAA) is associated with the proliferation and apoptosis of vascular smooth muscle cells (VSMCs). Our present study found that during HO or NaAsO induced injury of VSMC, the expression of miR-155-5p significantly increased. While silencing of miR-155-5p can attenuate HO or NaAsO suppressed viability and induced apoptosis of VSMCs. In silico analysis and western blot analysis suggested that miR-155-5p can suppress the expression of FOS and ZIC3 in VSMCs by targeting their 3'UTR. Over expression of FOS or ZIC3 can abolish HO treatment and miR-155-5p induced suppression of VSMC viability. The inhibitor of NF-κB (p65), while not STAT3, can abolish HO induced expression of miR-155-5p and cell apoptosis. In addition, HO treatment can increase the phosphorylation and nuclear translocation of p65 in VSMCs. The expression of miR-155-5p in cells isolated from participants diagnosed with AAA were significantly greater than that in the normal group. Further, miR-155-5p was negative correlated with the expression of FOS and ZIC3 in cells from AAA patients. Collectively, miR-155-5p can regulate the viability and apoptosis of VSMCs to trigger the progression of AAA. It might be an effective therapeutic target for the treatment of AAA in clinical practice.
作为最常见的主动脉瘤形式，腹主动脉瘤（AAA）与血管平滑肌细胞（VSMCs）的增殖和凋亡有关。我们目前的研究发现，在 HO 或 NaAsO 诱导的 VSMC 损伤中，miR-155-5p 的表达显著增加。而沉默 miR-155-5p 可以减轻 HO 或 NaAsO 对 VSMC 活力的抑制和诱导的凋亡。计算机分析和 Western blot 分析表明，miR-155-5p 可以通过靶向其 3'UTR 抑制 FOS 和 ZIC3 在 VSMCs 中的表达。FOS 或 ZIC3 的过表达可以消除 HO 处理和 miR-155-5p 诱导的 VSMC 活力抑制。NF-κB（p65）抑制剂，而不是 STAT3 抑制剂，可以消除 HO 诱导的 miR-155-5p 表达和细胞凋亡。此外，HO 处理可以增加 VSMCs 中 p65 的磷酸化和核转位。从诊断为 AAA 的患者中分离出的细胞中的 miR-155-5p 表达明显高于正常组。此外，miR-155-5p 与 AAA 患者细胞中 FOS 和 ZIC3 的表达呈负相关。总之，miR-155-5p 可以调节 VSMCs 的活力和凋亡，从而引发 AAA 的进展。它可能是临床实践中治疗 AAA 的有效治疗靶点。
