Porphyromonas gingivalis disrupts vascular endothelial homeostasis in a TLR-NF-κB axis dependent manner

Cardiovascular disease is still the leading cause of mortality worldwide.Vascular endothelial dysfunction is viewed as the initial step of most cardiovascular diseases.Many studies have indicated that periodontal pathogens,especially Porphyromonas gingivalis,are closely correlated with vascular endothelial homeostasis,but the function of P.gingivalis and the underlying mechanisms are still elusive.To illuminate the effects and elucidate the mechanisms of P.gingivalis on endothelial structural integrity,we developed P.gingivalis infection models in vivo and in vitro.Endothelial cell proliferation,differentiation and apoptosis were detected.Here,we showed that P.gingivalis can impair endothelial integrity by inhibiting cell proliferation and inducing endothelial mesenchymal transformation and apoptosis of endothelial cells,which reduce the cell levels and cause the endothelium to lose its ability to repair itself.A mechanistic analysis showed that TLR antagonist or NF-κB signalling inhibitor can largely rescue the damaged integrity of the endothelium caused by P.gingivalis,suggesting that TLR-NF-κB signalling plays a vital role in vascular endothelial homeostasis destroyed by P.gingivalis.These results suggest a potential intervention method for the prevention and treatment of cardiovascular disease.