While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is ac...While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, includingheart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment byperiodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate therelationship 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 autophagyinhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. Thisstudy also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomalsensitive 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 thangingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wildtype P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-typeP.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which arevirulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms thestrong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.展开更多
基金supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research (C) 20K08399 (to Yasuhiro Maejima)KAKENHI 19K18985,Grant-in-Aid for JSPS Fellows+1 种基金MSD Life Science FoundationPublic Interest Incorporated Foundation (to Yuka Shiheido-Watanabe)
文摘While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, includingheart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment byperiodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate therelationship 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 autophagyinhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. Thisstudy also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomalsensitive 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 thangingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wildtype P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-typeP.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which arevirulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms thestrong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.
