title: Proliferation of smooth muscle cells stimulated by Porphyromonas gingivalis is inhibited by apple polyphenol.
abstract: BACKGROUND
  Porphyromonas gingivalis (Pg) is thought to be involved in the progression of occlusive arterial lesions, whereas vascular smooth muscle cell (SMC) proliferation is considered to be involved in occlusive arterial disease. We previously showed that bacteremia caused by Pg infection induced proliferation of mouse aortic SMCs. Furthermore, human SMCs stimulated with human plasma incubated with Pg showed a marked transformation from the contractile to proliferative phenotype. In the present study, we examine the involvement of Pg gingipains and fimbriae in induction of the SMC transformation and proliferation, and effective inhibitors.
  
  
  METHODS
  Pg strains including gingipain- and fimbria-null mutants were incubated in human plasma, after which the bacteria were removed and the supernatants were added to cultured SMCs. To evaluate the effects of inhibitors, Pg organisms were incubated in plasma in the presence of apple polyphenol (AP), epigallocatechin gallate, KYT-1 (Arg-gingipain inhibitor), and KYT-36 (Lys-gingipain inhibitor).
  
  
  RESULTS
  Plasma supernatants from wild-type and fimbria-mutant cultures markedly stimulated cellular proliferation, whereas those containing gingipain-null mutants showed negligible effects. SMC proliferation was also induced by plasma treated with trypsin. Furthermore, plasma supernatants cultured in the presence of KYT-1/KYT-36 and AP showed significant inhibitory effects on SMC proliferation, whereas cultures with epigallocatechin gallate did not.
  
  
  CONCLUSIONS
  Our results suggest that Pg gingipains are involved in the induction of SMC transformation and proliferation, whereas this was inhibited by AP.
authors.affiliation: Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Osaka, Japan. hinaba@dent.osaka-u.ac.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Inaba
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Tagashira
authors.forename: Tomomasa
authors.initials: T
authors.lastname: Kanda
authors.forename: Atsuo
authors.initials: A
authors.lastname: Amano
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics; D001011:Aorta; D001157:Arterial Occlusive Diseases / Q000382:microbiology* / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002726:Chlorogenic Acid / Q000494:pharmacology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000235:genetics; D010861:Fimbriae, Bacterial / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology*; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009154:Mutation; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D016966:Porphyromonas gingivalis / Q000235:genetics; D011480:Protease Inhibitors / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013634:Tannins / Q000494:pharmacology*; D017539:Tunica Intima / Q000382:microbiology / Q000473:pathology
chemical_list: D018829:Adhesins, Bacterial; D017077:Culture Media, Conditioned; D005419:Flavonoids; D000080867:Gingipain Cysteine Endopeptidases; D010936:Plant Extracts; D011480:Protease Inhibitors; D013634:Tannins; C526219:apple polyphenol extract; D002726:Chlorogenic Acid; D002392:Catechin; C045651:epigallocatechin gallate; D003546:Cysteine Endopeptidases