Porphyromonas gingivalis infection alters Nrf2-phase II enzymes and nitric oxide in primary human aortic endothelial cells. Academic Article uri icon


  • BACKGROUND: Periodontal disease (PD) is known to be associated with endothelial dysfunction in patients with coronary artery and/or cardiovascular disease. In our study, we sought to explore the virulence of P. gingivalis (Pg) affecting glycogen synthase kinase 3 beta (GSK-3)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/tetrahydrobiopterin (BH4 )/ nitric oxide synthase (NOS) expression in primary human aortic endothelial cells (pHAECs). METHODS: pHAECs were infected for 48 hours with Pg in vitro using the Human oxygen-Bacteria anaerobic coculture technique. Cell viability was determined, and target gene expression changes were evaluated by quantitative real-time polymerase chain reaction at the end of each incubation period. RESULTS: Pg impaired pHAEC viability 24 hours post-infection. Pg infection reduced mRNA expression levels of endothelial NOS (eNOS), Nrf2, and Phase II enzymes (heme oxygenase-1, catalase, superoxide dismutase-1) in a time-dependent manner. Significant (P<0.05) increase in the inflammatory markers (interleukin [IL]-1, IL-6, and tumor necrosis factor-) were observed in the medium as well as in the infected cells. Interestingly, inducible NOS mRNA levels showed a significant (P<0.05) increase at 12 hours and 24 hours and were reduced at later time points. BH4 (cofactor of eNOS) biosynthesis enzyme dihydrofolate reductase (DHFR, salvage pathway) mRNA levels showed a significant (P<0.05) decrease, while mRNA levels of GSK-3 were elevated. CONCLUSIONS: These results suggest that periodontal bacterial infection may cause significant changes in the endothelial GSK-3/BH4 /eNOS/Nrf2 pathways, which may lead to impaired vascular relaxation. Greater understanding of the factors that adversely affect endothelial cell function could contribute to the development of new therapeutic compounds to treat PD-induced vascular diseases.

published proceedings

  • J Periodontol

altmetric score

  • 6.5

author list (cited authors)

  • Sampath, C., Okoro, E. U., Gipson, M. J., Chukkapalli, S. S., Farmer-Dixon, C. M., & Gangula, P. R.

citation count

  • 2

complete list of authors

  • Sampath, Chethan||Okoro, Emmanuel U||Gipson, Michael J||Chukkapalli, Sasanka S||Farmer-Dixon, Cherae M||Gangula, Pandu R

publication date

  • July 2021