P. Gingivalils Induces Endothelial Dysfunction By mPTP Via Mitochondrial Fission

To explore the important role of Drp1-VDAC1-HK2 axis in regulating mitochondrial permeability transition pore (mPTP) opening in Porphyromonas gingivalis (P. gingivalis)-induced endothelial dysfunction. First, analyze the changes in mitochondrial dynamics and mPTP structure-related genes in transcriptome sequencing data of HAECs after P. gingivalis infection. Second, observe the impact of mPTP opening on mitochondrial function in HAECs after P. gingivalis infection. Then, detect the changes in mitochondrial dynamics-related proteins in cellular, mitochondrial, and cytoplasmic fractions of HAECs after P. gingivalis infection by Western blot. Meanwhile, observe the binding of VDAC1 with p-Drp1 and HK2 under different conditions using co-immunoprecipitation and immunofluorescence. Establish an oral P. gingivalis-coated mouse model to detect various endothelial function indicators, including endothelium-dependent vasodilation. Transcriptome sequencing analysis shows significant down-regulation of mitochondrial dynamics and mPTP structure-related genes in HAECs after P. gingivalis infection. Cell experiments show that P. gingivalis infection leads to mitochondrial and endothelial dysfunction in HAECs. P. gingivalis infection promotes the mitochondrial translocation of p-Drp1 in HAECs, its binding to VDAC1, VDAC1 oligomerization, reduced binding of HK2 to VDAC1, and mPTP opening. Animal experiments show that oral P. gingivalis-coated mice have damaged aortic endothelium-dependent vasodilation function. However, CsA and Mdivi-1 can significantly alleviate P. gingivalis-induced endothelial dysfunction. P. gingivalis induces mPTP opening via the Drp1-VDAC1-HK2 axis, leading to mitochondrial dysfunction and contributing to endothelial dysfunction.