Toll-Like Receptor-2 Plays a Fundamental Role in Periodontal Bacteria-Accelerated Abdominal Aortic Aneurysms

Norio Aoyama; Jun-ichi Suzuki; Masahito Ogawa; Ryo Watanabe; Naho Kobayashi; Tomoya Hanatani; Norihiko Ashigaki; Asuka Sekinishi; Yuichi Izumi; Mitsuaki Isobe

doi:10.1253/circj.CJ-12-1191

Vascular Biology and Vascular Medicine

Toll-Like Receptor-2 Plays a Fundamental Role in Periodontal Bacteria-Accelerated Abdominal Aortic Aneurysms

Norio Aoyama, Jun-ichi Suzuki, Masahito Ogawa, Ryo Watanabe, Naho Kobayashi, Tomoya Hanatani, Norihiko Ashigaki, Asuka Sekinishi, Yuichi Izumi, Mitsuaki Isobe

Author information

Norio Aoyama
Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
Jun-ichi Suzuki
Department of Cardiovascular Medicine, Tokyo Medical and Dental University
Department of Advanced Clinical Science and Therapeutics, University of Tokyo
Masahito Ogawa
Department of Cardiovascular Medicine, Tokyo Medical and Dental University
Department of Advanced Clinical Science and Therapeutics, University of Tokyo
Ryo Watanabe
Department of Cardiovascular Medicine, Tokyo Medical and Dental University
Naho Kobayashi
Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
Tomoya Hanatani
Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
Norihiko Ashigaki
Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
Global Center of Excellence Program, “International Research Center for Molecular Science in Tooth and Bone Diseases”, Tokyo Medical and Dental University
Asuka Sekinishi
Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
Yuichi Izumi
Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
Global Center of Excellence Program, “International Research Center for Molecular Science in Tooth and Bone Diseases”, Tokyo Medical and Dental University
Mitsuaki Isobe
Department of Cardiovascular Medicine, Tokyo Medical and Dental University

Keywords: Aneurysm, Inflammation, Matrix metalloproteinase, Porphyromonas gingivalis, Toll-like receptor

JOURNAL FREE ACCESS

2013 Volume 77 Issue 6 Pages 1565-1573

DOI https://doi.org/10.1253/circj.CJ-12-1191

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Abstract

Background: Periodontopathic bacteria are detected at a high rate in specimens obtained from the aortic walls of patients with abdominal aortic aneurysm (AAA) and are involved in AAA development. The purpose of this study was to clarify the role of Toll-like receptors (TLRs), which are key receptors of virulence factors of many periodontal bacteria, on periodontopathic bacteria-accelerated AAA progression. Methods and Results: AAA was produced by peri-aortic application of 0.25mol/L CaCl₂, with NaCl used as a control. The mice were inoculated with live Porphyromonas (P.) gingivalis or vehicle once weekly. At 4 weeks after the application of CaCl₂, the aortic diameter of the P. gingivalis-infected wild-type mice showed a significant increase in comparison with vehicle control mice (P<0.05). The P. gingivalis-infected TLR-2 deficient mice showed no statistical increase in aortic diameter over the same period. The aortic diameter of the P. gingivalis-infected TLR-4 deficient mice statistically increased. Immunohistochemically, the levels of matrix metalloproteinase-2 and -9 in the aneurysmal samples from wild-type mice were higher than in TLR-2 deficient mice. Conclusions: P. gingivalis accelerated the progression of experimental AAA through TLR-2 signaling. (Circ J 2013; 77: 1565–1573)

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