Pg Promotes Atherosclerosis Through Endothelial Cell Pyroptosis Via Drp1-Mtros

In light of numerous studies that have established a correlation between periodontitis and atherosclerosis, this study aims to delve deeper into the specific mechanisms by which Porphyromonas gingivalis (Pg), the predominant causative agent of periodontitis, contributes to atherosclerosis. Male ApoE-/- mice were allowed to adapt for one week, and subsequently, Pg oral application and ligation of the maxillary molar using silk were administered to the mice. Mice was given a high-fat diet for 12 weeks. Plaque area was assessed using Oil Red O staining of aorta en face and aortic root, and mitochondrial reactive oxygen species (mtROS) production and pyroptosis were evaluated through fluorescence staining. In addition, a co-culture model of Pg and HAECs was established to assess mitochondrial morphology and function. Pyroptosis of HAECs was detected using Western blotting and flow cytometry. To observe the effect of mtROS on pyroptosis, Mito-TEMPO were used. To observe the effect of Drp1 on pyroptosis, small interfering RNA Drp1(Si-Drp1) and Mdivi-1 was used. Pg infection has been shown to induce damage to the mitochondria and pyroptosis of HAECs. Treatment with Mito-TEMPO, Si-Drp1 or Mdivi-1 alleviates mtROS production and pyroptosis. Similarly, compared with mice without Pg infection, we observed larger plaque size and much more pyroptosis in mice with Pg infection. These effects were also found to be mitigated by treatment with Mito-TEMPO or Mdivi-1. These results suggest that Pg upregulates Drp1, promotes mtROS production, leads to endothelial cell pyroptosis, and promotes atherosclerosis.