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Porphyromonas gingivalis as a Model Organism for Assessing Interaction of Anaerobic Bacteria with Host Cells
Published on: December 17, 2015
Porphyromonas gingivalis Induces Endothelial Dysfunction Through Sirt3-Dependent CypD Acetylation
Shengming Xu1, Cheng Zheng1, Jianmin Huang1
1Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, China.
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.
Insights
Porphyromonas gingivalis infection causes mitochondrial and endothelial dysfunction. Sirtuin 3 (Sirt3) activation reverses this damage by deacetylating Cyclophilin D (CypD), restoring cellular function.
Area of Science:
- Cardiovascular Biology
- Microbiology
- Mitochondrial Medicine
Background:
- Porphyromonas gingivalis (P. gingivalis) is linked to cardiovascular diseases.
- Endothelial dysfunction is a key factor in atherosclerosis and other cardiovascular pathologies.
- Mitochondrial dysfunction contributes to endothelial cell damage.
Purpose of the Study:
- To elucidate the mechanism by which P. gingivalis induces endothelial dysfunction.
- To investigate the role of Sirtuin 3 (Sirt3) in regulating mitochondrial function during P. gingivalis infection.
- To determine if Sirt3 activation can ameliorate P. gingivalis-induced cellular damage.
Main Methods:
- RNA sequencing to identify Sirtuin gene expression changes in P. gingivalis-infected human aortic endothelial cells (HAECs).
- Assessment of mitochondrial and endothelial function in HAECs treated with P. gingivalis and a Sirt3 agonist (Honokiol).
- Investigation of the Sirt3-Cyclophilin D (CypD) interaction using molecular biology techniques and evaluation of aortic vasorelaxation in infected mice.
Main Results:
- P. gingivalis infection led to mitochondrial and endothelial dysfunction in HAECs.
- Sirt3-dependent deacetylation of CypD at K167 was identified as a critical protective mechanism.
- In vivo studies showed P. gingivalis impaired vasodilation, disrupted endothelial integrity, and increased oxidative stress, all reversed by Sirt3 activation.
Conclusions:
- P. gingivalis infection induces mitochondrial and endothelial dysfunction.
- This dysfunction is mediated by a pathway involving Sirt3 and its deacetylation of CypD.
- Sirt3 activation represents a potential therapeutic strategy against P. gingivalis-associated vascular damage.
