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.

虽然之前的几项研究表明牙周病（PD）和心肌梗死（MI）之间存在联系，但其潜在机制仍不清楚。自噬是一种细胞质量控制过程，在包括心力衰竭在内的多种疾病中被激活，可以被牙龈卟啉单胞菌( Pg .) 抑制。然而，尚不确定牙周病原体引起的自噬损伤是否会刺激心肌梗死后心功能障碍的发展。因此，本研究旨在探讨PD与MI发展之间的关系，同时关注自噬的作用。用野生型Pg接种新生大鼠心肌细胞 (NRCM) 和 MI 模型小鼠。或牙龈蛋白酶缺乏的Pg。评估Pg抑制自噬的效果。接种野生型Pg的 NRCM 比接种缺乏牙龈蛋白酶的Pg的 NRCM 具有较低的细胞活力。这项研究还表明，牙龈蛋白酶可以在第 47 个赖氨酸残基处裂解囊泡相关膜蛋白 8 (VAMP8)（一种参与溶酶体敏感因子附着蛋白受体 (SNARE) 的蛋白质），从而抑制自噬。与缺乏牙龈蛋白酶的Pg接种的MI模型小鼠相比，野生型Pg接种的MI模型小鼠更容易发生心脏破裂，存活率和自噬活性较低。在给转基因MI模型小鼠（VAMP8-K47A）接种野生型Pg .后，与接种野生型Pg .的MI模型小鼠相比，它们表现出显着增加的自噬激活，从而抑制了心脏破裂并提高了总体存活率。这些发现表明牙龈蛋白酶（Pg的毒力因子）通过裂解 VAMP8 和破坏自噬来损害梗塞心肌。这项研究证实了 PD 和 MI 之间的密切关联，并为自噬在这种关系中的潜在作用提供了新的见解。