Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis, has been shown to accelerate the progression of atherosclerosis (AS). However, the definite mechanisms remain elusive. Emerging evidence supports an association between mitochondrial dysfunction and AS. In our study, the impact of P. gingivalis on mitochondrial dysfunction and the potential mechanism were investigated. The mitochondrial morphology of EA.hy926 cells infected with P. gingivalis was assessed by transmission electron microscopy, mitochondrial staining, and quantitative analysis of the mitochondrial network. Fluorescence staining and flow cytometry analysis were performed to determine mitochondrial reactive oxygen species (mtROS) and mitochondrial membrane potential (MMP) levels. Cellular ATP production was examined by a luminescence assay kit. The expression of key fusion and fission proteins was evaluated by western blot and immunofluorescence. Mdivi-1, a specific Drp1 inhibitor, was used to elucidate the role of Drp1 in mitochondrial dysfunction. Our findings showed that P. gingivalis infection induced mitochondrial fragmentation, increased the mtROS levels, and decreased the MMP and ATP concentration in vascular endothelial cells. We observed upregulation of Drp1 (Ser616) phosphorylation and translocation of Drp1 to mitochondria. Mdivi-1 blocked the mitochondrial fragmentation and dysfunction induced by P. gingivalis. Collectively, these results revealed that P. gingivalis infection promoted mitochondrial fragmentation and dysfunction, which was dependent on Drp1. Mitochondrial dysfunction may represent the mechanism by which P. gingivalis exacerbates atherosclerotic lesions.

牙龈卟啉单胞菌( P. gingivalis ) 是牙周炎的关键病原体，已被证明可加速动脉粥样硬化 (AS) 的进展。然而，确切的机制仍然难以捉摸。新出现的证据支持线粒体功能障碍和 AS 之间的关联。在我们的研究中，研究了牙龈卟啉单胞菌对线粒体功能障碍的影响及其潜在机制。牙龈卟啉单胞菌感染EA.hy926细胞的线粒体形态通过透射电子显微镜、线粒体染色和线粒体网络的定量分析来评估。进行荧光染色和流式细胞术分析以确定线粒体活性氧 (mtROS) 和线粒体膜电位 (MMP) 水平。通过发光测定试剂盒检查细胞ATP产生。通过蛋白质印迹和免疫荧光评估关键融合和裂变蛋白的表达。Mdivi-1 是一种特异性 Drp1 抑制剂，用于阐明 Drp1 在线粒体功能障碍中的作用。我们的研究结果表明，P。牙龈炎感染诱导线粒体断裂，增加 mtROS 水平，并降低血管内皮细胞中 MMP 和 ATP 浓度。我们观察到 Drp1 (Ser616) 磷酸化的上调和 Drp1 向线粒体的易位。Mdivi-1 阻断了由P诱导的线粒体断裂和功能障碍。牙龈炎。总的来说，这些结果表明P。gingivalis感染促进线粒体断裂和功能障碍，这依赖于 Drp1。线粒体功能障碍可能代表了P的机制。牙龈炎会加剧动脉粥样硬化病变。