title: Porphyromonas gingivalis, a periodontal pathogen, enhances myocardial vulnerability, thereby promoting post-infarct cardiac rupture.
abstract: There is a strong association between periodontal disease (PD) and atherosclerosis. However, it remains unknown whether PD is also involved in myocardial damage. We hypothesized that infection with periodontal pathogens could cause an adverse outcome after myocardial infarction (MI). C57BL/6J mice were inoculated with Porphyromonas gingivalis (P.g.), a major periodontal pathogen, or injected with phosphate-buffered saline (PBS) into a subcutaneously-implanted steelcoil chamber before and after coronary artery ligation. A significant increase in mortality, due to cardiac rupture, was observed in the P.g.-inoculated MI mice. Ultrastructural examinations revealed that P.g. invaded the ischemic myocardium of the P.g.-inoculated MI mice. The expression of p18 Bax, an active form of pro-apoptotic Bax protein, markedly increased in the P.g.-inoculated MI hearts. In vitro experiments demonstrated that gingipain, a protease uniquely secreted from P.g., cleaved wild type Bax at Arg34, as evidenced by the observation that the cleavage of Bax by gingipain was completely abolished by the Arg34Ala mutation in Bax. Treatment with immunoglobulin Y against gingipain significantly decreased the mortality of the P.g.-inoculated MI mice caused by cardiac rupture. Furthermore, inoculation of P.g. also resulted in an increase of MMP-9 activity in the post-MI myocardium by enhancing oxidative stress, possibly through impairing the selective autophagy-mediated clearance of damaged mitochondria. In conclusion, infection with P.g. during MI plays a detrimental role in the healing process of the infarcted myocardium by invasion of P.g. into the myocardium, thereby promoting apoptosis and the MMP-9 activity of the myocardium, which, in turn, causes cardiac rupture.
authors.affiliation: Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Shiheido
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maejima
authors.affiliation: Department of Advanced Clinical Sciences and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Suzuki
authors.affiliation: Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Aoyama
authors.affiliation: Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Sakamaki
authors.affiliation: Department of Advanced Clinical Sciences and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Wakayama
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: Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shizuko
authors.initials: S
authors.lastname: Ichinose
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, Graduate School of Medical and Dental Sciences, 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. Electronic address: isobemi.cvm@tmd.ac.jp.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D000818:Animals; D017209:Apoptosis; D016866:Bacteroidaceae Infections / Q000150:complications* / Q000382:microbiology*; D004195:Disease Models, Animal; D004452:Echocardiography; D006342:Heart Rupture, Post-Infarction / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000648:ultrastructure; D018384:Oxidative Stress; D016966:Porphyromonas gingivalis; D051381:Rats; D015996:Survival Rate; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051028:bcl-2-Associated X Protein; D020780:Matrix Metalloproteinase 9
keywords: Apoptosis; Autophagy; Infectious disease; Myocardial infarction; Oxidative stress