A Chinese herbal formula "Gan-Lu-Yin" suppresses vascular smooth muscle cell migration by inhibiting matrix metalloproteinase-2/9 through the PI3K/AKT and ERK signaling pathways

BMC Complement Altern Med. 2012 Aug 24;12:137. doi: 10.1186/1472-6882-12-137.

Abstract

Background: This study was to explore the effects of Gan-Lu-Yin (GLY) on the migration of vascular smooth muscle cells (VSMCs) induced by fetal bovine serum and on neointima formation in a rat model of carotid artery balloon injury.

Methods: VSMCs were treated with different concentrations of GLY, and then analyzed with Flow cytometric analysis, zymography, transwell, and western blotting. SD rats received balloon-injury were analyzed with H&E staining.

Results: Our results showed that GLY significantly decreased the thickness of neointima. The inhibition by non-cytoxic doses of GLY of VSMCs migration was through its negative regulatory effects on phosphorylated ERK1/2, PI3K/AKT, and FAK. The data showed that GLY can inhibit the migration of VSMCs cells, and might block injury-induced neointima hyperplasia via the inhibition of VSMCs migration, without inducing apoptosis.

Conclusions: These observations provide a mechanism of GLY in attenuating cell migration, thus as a potential intervention for restenosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Down-Regulation / drug effects*
  • Drugs, Chinese Herbal / pharmacology*
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / enzymology
  • Myocytes, Smooth Muscle / cytology*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / enzymology
  • Neointima / drug therapy
  • Neointima / enzymology
  • Neointima / physiopathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats

Substances

  • Drugs, Chinese Herbal
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9