Porphyromonas gingivalis, a periodontal pathogen, enhances myocardial vulnerability, thereby promoting post-infarct cardiac rupture. (October 2016)

• Record Type: Journal Article
• Authors: Shiheido, Yuka; Maejima, Yasuhiro; Suzuki, Jun-ichi; Aoyama, Norio; Kaneko, Makoto; Watanabe, Ryo; Sakamaki, Yuriko; Wakayama, Kouji; Ikeda, Yuichi; Akazawa, Hiroshi; Ichinose, Shizuko; Komuro, Issei; Izumi, Yuichi; Isobe, Mitsuaki
• Is Part Of: Journal of molecular and cellular cardiology. Volume 99(2016:Oct.)
• Page Start: 123
• Page End: 137
• Publication Date: 2016-10
• Subjects: Myocardial infarction -- Infectious disease -- Apoptosis -- Oxidative stress -- Autophagy; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2016.03.017
• Languages: English
• ISSNs: 0022-2828

Abstract

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. Graphical abstract: Highlights: Infection with Porphyromonas gingivalis ( P.g. ) promotes cardiac rupture after MI. P.g. invades the ischemic myocardium. Infection with P.g. promotes the accumulation of p18 Bax. Gingipains from P.g. activate Bax and promote cardiomyocyte apoptosis. Infection with P.g. promotes oxidative stress and MMP-9 protein level and activity.