Porphyromonas gingivalis Induces Endothelial Dysfunction Through Sirt3-Dependent CypD Acetylation

Abstract

Aims: To investigate how Porphyromonas gingivalis induces endothelial dysfunction, focusing on the regulatory role of Sirtuin 3 (Sirt3) in mitochondrial function. Methods: 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. Results: 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. Conclusion: The present study demonstrated that P. gingivalis induced mitochondrial and endothelial dysfunction, which was mediated through Sirt3-dependent CypD deacetylation.