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• W4380680003 abstract "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 gingipain-deficient P.g.-inoculated NRCMs. The study also found that gingipain cleaves vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomal sensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, 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. Genetically modified MI model mice (VAMP8-K47A) were inoculated with wild-type P.g., and they exhibited significantly increased autophagy activation compared to wild-type P.g.-inoculated MI model mice, which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, 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 insight into the potential role of autophagy in this relationship." @default.
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• W4380680003 date "2023-06-15" @default.
• W4380680003 modified "2023-10-14" @default.
• W4380680003 title "Porphyromonas gingivalis, a periodontal pathogen, Impairs Post-infarcted Myocardium by Inhibiting Autophagosome–Lysosome Fusion" @default.
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• W4380680003 doi "https://doi.org/10.21203/rs.3.rs-3029636/v1" @default.
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