Department of Vascular Surgery, General Hospital of People's Liberation Army, Beijing 100853, P.R. China.
Department of Cardiology, Xi'an No. 3 Hospital, Xi'an, Shaanxi 710018, P.R. China.
Int J Mol Med. 2018 Apr;41(4):2350-2358. doi: 10.3892/ijmm.2018.3426. Epub 2018 Jan 25.
In the present study, the function of microRNA (miR)‑195 on abdominal aortic aneurysm (AAA) and its possible mechanism were investigated. Reverse transcription‑quantitative polymerase chain reaction analysis was used to detect the expression of miR‑195 in patients with AAA. The expression levels of miR‑195 in patients with AAA were effectively increased. The present study also used miR‑195 mimics to increase the expression of miR‑195, and ELISA kits and western blot analysis were used to analyze the levels of interleukin (IL)‑1β and IL‑6, and the protein expression levels of matrix metalloproteinase (MMP)‑2, MMP‑9, tumor necrosis factor (TNF)‑α, nuclear factor (NF)‑κB, vascular endothelial growth factor (VEGF), phosphoinositide 3‑kinase (PI3K) and phosphorylated (p‑)Akt. The overexpression of miR‑195 promoted the levels of IL‑1β and IL‑6, induced the protein expression of MMP‑2 and MMP‑9, upregulated the protein expression of TNF‑α and NF‑κB, and suppressed the protein expression levels of VEGF, PI3K and p‑Akt in angiotensin II‑vascular smooth muscle cells. In addition, TNF‑α promoted the pre‑inflammatory effect of miR‑195 on the protein expression levels of TNF‑α and NF‑κB, levels of IL‑1β and IL‑6, and protein expression levels of MMP‑2 and MMP‑9 in the angiotensin II‑vascular smooth muscle cells. Suppression of PI3K promoted the pre‑inflammatory effect of miR‑195 on the protein expression of PI3K, p‑Akt and VEGF, the levels of IL‑1β and IL‑6, and the protein expression of MMP‑2 and MMP‑9 in angiotensin II‑vascular smooth muscle cells. Combined, these results suggested that miR‑195 suppressed AAA inflammation through the TNF‑α/NF‑κB and VEGF/PI3K/Akt pathways.
在本研究中,研究了 microRNA (miR) -195 在腹主动脉瘤 (AAA) 中的功能及其可能的机制。逆转录-定量聚合酶链反应分析用于检测 AAA 患者中 miR-195 的表达。miR-195 在 AAA 患者中的表达水平得到有效上调。本研究还使用 miR-195 模拟物增加 miR-195 的表达,并用 ELISA 试剂盒和 Western blot 分析检测白细胞介素 (IL) -1β 和 IL-6 的水平,以及基质金属蛋白酶 (MMP) -2、MMP-9、肿瘤坏死因子 (TNF) -α、核因子 (NF) -κB、血管内皮生长因子 (VEGF)、磷酸肌醇 3-激酶 (PI3K) 和磷酸化 (p-)Akt 的蛋白表达水平。miR-195 的过表达促进了 IL-1β 和 IL-6 的水平,诱导了 MMP-2 和 MMP-9 的蛋白表达,上调了 TNF-α和 NF-κB 的蛋白表达,并抑制了血管紧张素 II-血管平滑肌细胞中 VEGF、PI3K 和 p-Akt 的蛋白表达水平。此外,TNF-α促进了 miR-195 对 TNF-α和 NF-κB 的蛋白表达水平、IL-1β 和 IL-6 的水平以及 MMP-2 和 MMP-9 的蛋白表达水平的促炎作用。抑制 PI3K 促进了 miR-195 对 PI3K、p-Akt 和 VEGF 的蛋白表达、IL-1β 和 IL-6 的水平以及 MMP-2 和 MMP-9 的蛋白表达的促炎作用。综上所述,miR-195 通过 TNF-α/NF-κB 和 VEGF/PI3K/Akt 通路抑制 AAA 炎症。