Ginkgolide A-gold nanoparticles inhibit vascular smooth muscle proliferation and migration in vitro and reduce neointimal hyperplasia in a mouse model

J Surg Res. 2011 Nov;171(1):31-9. doi: 10.1016/j.jss.2011.03.018. Epub 2011 Apr 1.


Background: Neointimal formation is mediated by phenotypic changes in vascular smooth muscle cells (SMC) and is an important mediator of restenosis following arterial reconstruction. We conjugated antioxidant ginkgolide A (GA) to gold nanoparticles (GNP) to determine the effect of GA delivery on neointimal formation.

Materials and methods: GA was conjugated to 80 nm GNP in an overnight incubation. Mouse P53LMAC01 vascular SMC were treated with various doses of GA-GNP, GA alone, GNP alone, and no treatment control. Cell proliferation and migration were analyzed, and superoxide anion levels and the phosphorylation status of ERK1/2 were determined. Mice underwent ligation of the common carotid artery along with local treatment with GNP (control) or GA-GNP. The carotid artery was harvested and subjected to immunohistochemical analysis.

Results: GA-GNP treatment significantly inhibited SMC proliferation and migration in vitro in comparison to GNP treatment alone, and the effect persisted for up to 72 h after treatment. Treatment with GA-GNP also reduced superoxide anion levels in vitro. PDGF-BB substantially induced ERK1/2 phosphorylation in GNP control cells; this PDGE-BB induced ERK1/2 phosphorylation was significantly inhibited in GA-GNP-treated cells compared with GNP only. GA-GNP significantly reduced neointimal hyperplasia after injury in mice, and proliferating cell nuclear antigen (PCNA) staining was reduced substantially in the arteries of mice treated with GA-GNP.

Conclusions: GA-GNP reduce vascular SMC proliferation and migration in vitro through reduced activation of ERK1/2. Local treatment with GA-GNP in areas of arterial injury reduced neointimal hyperplasia and subsequent stenosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Disease Models, Animal
  • Ginkgolides / pharmacology*
  • Gold / pharmacology*
  • Hyperplasia / drug therapy
  • In Vitro Techniques
  • Lactones / pharmacology*
  • Metal Nanoparticles / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Muscle, Smooth, Vascular / pathology*
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / pathology
  • Neointima / drug therapy*
  • Neointima / pathology
  • Platelet-Derived Growth Factor / pharmacology
  • Superoxides / antagonists & inhibitors


  • Ginkgolides
  • Lactones
  • Platelet-Derived Growth Factor
  • Superoxides
  • Gold
  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • ginkgolide A