Xu Shengming, Zheng Cheng, Huang Jianmin, Lu Bin, Que Hanxin, Xu Leyan, Hou Yubo, He Linlin, Fan Xia, Deng Ke, Hu Rongdang, Deng Hui, Wang Yi
Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Periodontology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, China.
J Periodontal Res. 2025 May 9. doi: 10.1111/jre.13416.
To investigate how Porphyromonas gingivalis induces endothelial dysfunction, focusing on the regulatory role of Sirtuin 3 (Sirt3) in mitochondrial function.
Differentially expressed Sirtuin family genes in P. gingivalis-infected human aortic endothelial cells (HAECs) were identified through RNA sequencing and validated by quantitative real-time PCR and Western blot. Mitochondrial and endothelial functions were assessed in P. gingivalis-infected HAECs with or without Sirt3-specific agonist Honokiol. Cyclophilin D (CypD) K167 point mutation plasmids were constructed, and Co-immunoprecipitation was performed to investigate the Sirt3-CypD interaction. The vasorelaxation of aortas from mice orally administrated with P. gingivalis was also evaluated.
Porphyromonas gingivalis infection in HAECs resulted in mitochondrial and endothelial dysfunction. Mechanistic studies revealed that Sirt3-mediated deacetylation of CypD at K167 was pivotal in alleviating P. gingivalis-induced mitochondrial and endothelial dysfunction. Oral inoculation of P. gingivalis in mice significantly impaired endothelial-dependent vasodilation, disrupted aortic endothelial integrity, increased endothelial cell apoptosis, and elevated mitochondrial reactive oxygen species production. Notably, Sirt3 activation reversed mitochondrial and endothelial dysfunction induced by P. gingivalis both in vivo and in vitro.
The present study demonstrated that P. gingivalis induced mitochondrial and endothelial dysfunction, which was mediated through Sirt3-dependent CypD deacetylation.
研究牙龈卟啉单胞菌如何诱导内皮功能障碍，重点关注沉默调节蛋白3（Sirt3）在线粒体功能中的调节作用。
通过RNA测序鉴定牙龈卟啉单胞菌感染的人主动脉内皮细胞（HAECs）中差异表达的沉默调节蛋白家族基因，并通过定量实时PCR和蛋白质免疫印迹法进行验证。在有或没有Sirt3特异性激动剂厚朴酚的情况下，评估牙龈卟啉单胞菌感染的HAECs中的线粒体和内皮功能。构建亲环蛋白D（CypD）K167点突变质粒，并进行免疫共沉淀以研究Sirt3与CypD的相互作用。还评估了口服牙龈卟啉单胞菌的小鼠主动脉的血管舒张情况。
牙龈卟啉单胞菌感染HAECs导致线粒体和内皮功能障碍。机制研究表明，Sirt3介导的CypD在K167位点的去乙酰化在减轻牙龈卟啉单胞菌诱导的线粒体和内皮功能障碍中起关键作用。小鼠口服接种牙龈卟啉单胞菌会显著损害内皮依赖性血管舒张，破坏主动脉内皮完整性，增加内皮细胞凋亡，并提高线粒体活性氧的产生。值得注意的是，Sirt3激活在体内和体外均可逆转牙龈卟啉单胞菌诱导的线粒体和内皮功能障碍。
本研究表明，牙龈卟啉单胞菌诱导线粒体和内皮功能障碍，这是通过Sirt3依赖的CypD去乙酰化介导的。
