Toll-like receptor 4 signaling has a critical role in Porphyromonas gingivalis-accelerated neointimal formation after arterial injury in mice

Hypertens Res. 2016 Oct;39(10):717-722. doi: 10.1038/hr.2016.58. Epub 2016 May 26.

Abstract

Recently, we reported that a periodontopathic pathogen, Porphyromonas gingivalis (P. gingivalis), infection induced neointimal hyperplasia with enhanced expression of monocyte chemoattractant protein (MCP)-1 after arterial injury in wild-type mice. Toll-like receptor (TLR) 4 is known to be a key receptor for virulence factors of P. gingivalis. The aim of this study is to assess the hypothesis that TLR4 has a critical role in periodontopathic bacteria-induced neointimal formation after an arterial injury. Wild-type and TLR4-deficient mice were used in this study. The femoral arteries were injured, and P. gingivalis or vehicle was injected subcutaneously once per week. Fourteen days after arterial injury, murine femoral arteries were obtained for histopathological and immunohistochemical analyses. The anti-P. gingivalis IgG levels in P. gingivalis-infected groups were significantly increased compared with the anti-P. gingivalis IgG levels of the corresponding non-infected groups in both wild-type and TLR4-deficient mice. TLR4 deficiency negated P. gingivalis-induced neointimal formation compared with that observed in wild-type mice and reduced the number of MCP-1 positive cells in the neointimal area. We conclude that P. gingivalis infection may promote neointimal formation after an arterial injury through TLR4 signaling.

MeSH terms

  • Animals
  • Bacteroidaceae Infections / metabolism
  • Bacteroidaceae Infections / microbiology*
  • Femoral Artery / injuries*
  • Femoral Artery / metabolism
  • Femoral Artery / microbiology
  • Mice
  • Mice, Knockout
  • Neointima / metabolism
  • Neointima / microbiology*
  • Porphyromonas gingivalis*
  • Signal Transduction / physiology*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Toll-Like Receptor 4