title: Infection with Porphyromonas gingivalis exacerbates endothelial injury in obese mice.
abstract: BACKGROUND
  A number of studies have revealed a link between chronic periodontitis and cardiovascular disease in obese patients. However, there is little information about the influence of periodontitis-associated bacteria, Porphyromonas gingivalis (Pg), on pathogenesis of atherosclerosis in obesity.
  
  
  METHODS
  In vivo experiment: C57BL/6J mice were fed with a high-fat diet (HFD) or normal chow diet (CD), as a control. Pg was infected from the pulp chamber. At 6 weeks post-infection, histological and immunohistochemical analysis of aortal tissues was performed. In vitro experiment: hTERT-immortalized human umbilical vein endothelial cells (HuhT1) were used to assess the effect of Pg/Pg-LPS on free fatty acid (FFA) induced endothelial cells apoptosis and regulation of cytokine gene expression.
  
  
  RESULTS
  Weaker staining of CD31 and increased numbers of TUNEL positive cells in aortal tissue of HFD mice indicated endothelial injury. Pg infection exacerbated the endothelial injury. Immunohistochemically, Pg was detected deep in the smooth muscle of the aorta, and the number of Pg cells in the aortal wall was higher in HFD mice than in CD mice. Moreover, in vitro, FFA treatment induced apoptosis in HuhT1 cells and exposure to Pg-LPS increased this effect. In addition, Pg and Pg-LPS both attenuated cytokine production in HuhT1 cells stimulated by palmitate.
  
  
  CONCLUSIONS
  Dental infection of Pg may contribute to pathogenesis of atherosclerosis by accelerating FFA-induced endothelial injury.
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; Department of Pediatric Dentistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Ao
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Miyauchi
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Inubushi
authors.affiliation: Center of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima University, Hiroshima, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Kitagawa
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Furusho
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ando
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Nurina Febriyanti
authors.initials: NF
authors.lastname: Ayuningtyas
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Nagasaki
authors.affiliation: Department of Microbiology, Tokyo Dental College, Tokyo, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ishihara
authors.affiliation: Department of Cellular and Molecular Biology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tahara
authors.affiliation: Department of Pediatric Dentistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kozai
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
mesh_terms: D000818:Animals; D001011:Aorta / Q000382:microbiology / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009130:Muscle, Smooth / Q000382:microbiology / Q000473:pathology; D010168:Palmitates / Q000633:toxicity; D010518:Periodontitis / Q000382:microbiology* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000302:isolation & purification; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D010168:Palmitates; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2