Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome-lysosome fusion.

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2023-09-18 DOI:10.1038/s41368-023-00251-2
Yuka Shiheido-Watanabe, Yasuhiro Maejima, Shun Nakagama, Qintao Fan, Natsuko Tamura, Tetsuo Sasano
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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.

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牙龈卟啉单胞菌是一种牙周病原体,通过抑制自噬体-溶酶体融合来损害梗死后的心肌。
尽管先前的几项研究表明牙周病(PD)和心肌梗死(MI)之间存在联系,但其潜在机制尚不清楚。自噬是一种在包括心力衰竭在内的多种疾病中被激活的细胞质量控制过程,可被牙龈卟啉单胞菌(P.g.)抑制。然而,尚不确定牙周病原体的自噬损伤是否会刺激MI后心脏功能障碍的发展。因此,本研究旨在探讨PD与MI发展之间的关系,同时重点研究自噬的作用。新生大鼠心肌细胞(NRCMs)和MI模型小鼠接种野生型P.g.或银杏素缺乏型P.g.以评估P.g.对自噬的抑制作用。野生型P.g.-接种的NRCMs的细胞活力低于接种银杏素缺乏的P.g.。本研究还揭示了银杏素可以切割囊泡相关膜蛋白8(VAMP8),一种参与溶酶体敏感因子附着蛋白受体(SNARE)的蛋白质,位于第47赖氨酸残基,从而抑制自噬。野生型P.g.接种的MI模型小鼠更容易发生心脏破裂,其存活率和自噬活性低于银杏叶素缺乏的P.g.接种MI模型小鼠。用野生型P.g.接种转基因MI模型小鼠(VAMP8-K47A)后,与接种野生型P.g.的MI模型小鼠相比,它们表现出显著增加的自噬激活,这抑制了心脏破裂并提高了总生存率。这些发现表明,银杏蛋白酶是P.g.的毒力因子,通过裂解VAMP8和破坏自噬来损害梗死心肌。这项研究证实了PD和MI之间的强烈关联,并为自噬在这种关系中的潜在作用提供了新的见解。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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