title: Toll-like receptor-2 has a critical role in periodontal pathogen-induced myocardial fibrosis in the pressure-overloaded murine hearts.
abstract: Recent studies have indicated that periodontopathic bacteria might accelerate the development of cardiac fibrosis. Porphyromonas gingivalis (P. gingivalis), a major periodontal bacterium, is mainly recognized by Toll-like receptor-2 (TLR-2). However, the role of TLR-2 in the acceleration of cardiac fibrosis via infections caused by periodontal bacteria has not yet been investigated. Here we investigated the role TLR-2 has in periodontal pathogen-induced cardiac fibrosis. TLR-2 knockout (KO) and wild type (WT) male C57BL/6 mice were subjected to a transverse aortic constriction (TAC) surgical procedure 2 weeks after chamber implantation. After the TAC operation, mice received injections once a week of P. gingivalis or vehicle into the chambers that were implanted in the back of mice. Fractional shortening (FS) was measured using echocardiography 1 week after the TAC surgical procedure. Four weeks after the TAC surgical procedure, blood and heart samples were collected. FS in the infected group of WT mice was significantly lower than in mice that received sham operations; however, FS in the uninfected group did not decrease in a similar manner to that in the infected group. Cardiac fibrosis was significantly enhanced in TAC-operated WT mice infected with P. gingivalis (n=14), whereas it was inhibited in TAC-operated TLR-2 KO mice infected with P. gingivalis (n=7). The level of matrix metalloproteinase-2 (MMP-2) mRNA was higher in WT mice infected with P. gingivalis compared with non-infected WT mice. However, the level of MMP-2 mRNA was significantly lower in TLR-2 KO mice compared with that in WT mice. In conclusion, TLR-2 had a critical role in the development of cardiac fibrosis under the conditions of pressure overload and periodontal pathogen infection.
authors: Department of Periodontology, The University of Tokyo, Tokyo, Japan.
authors: Makoto
authors: M
authors: Kaneko
authors: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors: Jun-Ichi
authors: JI
authors: Suzuki
authors: Department of Periodontology, The University of Tokyo, Tokyo, Japan.
authors: Norio
authors: N
authors: Aoyama
authors: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Ryo
authors: R
authors: Watanabe
authors: Department of Periodontology, The University of Tokyo, Tokyo, Japan.
authors: Asuka
authors: A
authors: Yoshida
authors: Department of Periodontology, The University of Tokyo, Tokyo, Japan.
authors: Yuka
authors: Y
authors: Shiheido
authors: Department of Periodontology, The University of Tokyo, Tokyo, Japan.
authors: Yuichi
authors: Y
authors: Izumi
authors: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Mitsuaki
authors: M
authors: Isobe
mesh_terms: D000818:Animals; D016866:Bacteroidaceae Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006332:Cardiomegaly / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D004452:Echocardiography; D005355:Fibrosis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D006321:Heart / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D016966:Porphyromonas gingivalis; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051195:Toll-Like Receptor 2