title: Toll-like receptor 4 signaling has a critical role in Porphyromonas gingivalis-accelerated neointimal formation after arterial injury in mice.
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.
authors.affiliation: Department of Periodontology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Naho
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Suzuki
authors.affiliation: Department of Periodontology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Aoyama
authors.affiliation: Department of Periodontology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Shouta
authors.initials: S
authors.lastname: Akimoto
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Wakayama
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kumagai
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akazawa
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.affiliation: Department of Periodontology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D000818:Animals; D016866:Bacteroidaceae Infections / Q000378:metabolism / Q000382:microbiology*; D005263:Femoral Artery / Q000293:injuries* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D058426:Neointima / Q000378:metabolism / Q000382:microbiology*; D016966:Porphyromonas gingivalis; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051197:Toll-Like Receptor 4