miR-195 suppresses abdominal aortic aneurysm through the TNF-α/NF-κB and VEGF/PI3K/Akt pathway

Int J Mol Med. 2018 Apr;41(4):2350-2358. doi: 10.3892/ijmm.2018.3426. Epub 2018 Jan 25.

Abstract

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.

MeSH terms

  • Aged
  • Aortic Aneurysm, Abdominal / genetics*
  • Aortic Aneurysm, Abdominal / immunology
  • Aortic Aneurysm, Abdominal / pathology
  • Down-Regulation
  • Gene Expression Regulation*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / immunology
  • Middle Aged
  • Muscle, Smooth, Vascular / immunology
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / immunology
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / immunology
  • Signal Transduction*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / immunology

Substances

  • MIRN195 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt