Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome–lysosome fusion
Abstract While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), the underlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, including heart failure, can be suppressed b...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-09-01
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| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-023-00251-2 |
| _version_ | 1827724185127878656 |
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| author | Yuka Shiheido-Watanabe Yasuhiro Maejima Shun Nakagama Qintao Fan Natsuko Tamura Tetsuo Sasano |
| author_facet | Yuka Shiheido-Watanabe Yasuhiro Maejima Shun Nakagama Qintao Fan Natsuko Tamura Tetsuo Sasano |
| author_sort | Yuka Shiheido-Watanabe |
| collection | DOAJ |
| description | Abstract While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), the underlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, including heart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment by periodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate the relationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes (NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagy inhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. This study also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomal sensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity than gingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wild-type P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-type P.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which are virulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms the strong association between PD and MI and provides new insights into the potential role of autophagy in this relationship. |
| first_indexed | 2024-03-10T22:12:10Z |
| format | Article |
| id | doaj.art-369749cddac847ed881a0a1daec41f8c |
| institution | Directory Open Access Journal |
| issn | 2049-3169 |
| language | English |
| last_indexed | 2024-03-10T22:12:10Z |
| publishDate | 2023-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | International Journal of Oral Science |
| spelling | doaj.art-369749cddac847ed881a0a1daec41f8c2023-11-19T12:34:05ZengNature Publishing GroupInternational Journal of Oral Science2049-31692023-09-0115111510.1038/s41368-023-00251-2Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome–lysosome fusionYuka Shiheido-Watanabe0Yasuhiro Maejima1Shun Nakagama2Qintao Fan3Natsuko Tamura4Tetsuo Sasano5Department of Cardiovascular Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental UniversityDepartment of Cardiovascular Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental UniversityDepartment of Cardiovascular Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental UniversityDepartment of Cardiovascular Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental UniversityDepartment of Cardiovascular Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental UniversityDepartment of Cardiovascular Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental UniversityAbstract While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), the underlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, including heart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment by periodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate the relationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes (NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagy inhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. This study also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomal sensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity than gingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wild-type P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-type P.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which are virulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms the strong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.https://doi.org/10.1038/s41368-023-00251-2 |
| spellingShingle | Yuka Shiheido-Watanabe Yasuhiro Maejima Shun Nakagama Qintao Fan Natsuko Tamura Tetsuo Sasano Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome–lysosome fusion International Journal of Oral Science |
| title | Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome–lysosome fusion |
| title_full | Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome–lysosome fusion |
| title_fullStr | Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome–lysosome fusion |
| title_full_unstemmed | Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome–lysosome fusion |
| title_short | Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome–lysosome fusion |
| title_sort | porphyromonas gingivalis a periodontal pathogen impairs post infarcted myocardium by inhibiting autophagosome lysosome fusion |
| url | https://doi.org/10.1038/s41368-023-00251-2 |
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