Porphyromonas gingivalis infection upregulates the endothelin (ET) system in brain microvascular endothelial cells

Can J Physiol Pharmacol. 2022 Jul 1;100(7):679-688. doi: 10.1139/cjpp-2022-0035. Epub 2022 Apr 20.


Endothelin-1 (ET-1), the most potent vasoconstrictor identified to date, contributes to cerebrovascular dysfunction and brain ET-1 levels were shown to be related to Alzheimer's disease and related dementias (ADRD) progression. ET-1 also contributes to neuroinflammation, especially in infections of the central nervous system. Recent studies causally linked chronic periodontal infection with an opportunistic anaerobic bacterium Porphyromonas gingivalis (Coykendall et al.) Shah & Collins to AD development. Thus, the goal of the study was to determine the impact of P. gingivalis infection on the ET system and cell senescence in brain microvascular endothelial cells. Cells were infected with a multiplicity of infection 50 P. gingivalis with and without extracellular ATP-induced oxidative stress for 24 h. Cell lysates were collected for analysis of endothelin A receptor (ETA)/endothelin B receptor (ETB) receptor as well as senescence markers. ET-1 levels in cell culture media were measured with enzyme-linked immunosorbent assay. P. gingivalis infection increased ET-1 (pg/mL) secretion, as well as the ETA receptor expression, whereas decreased lamin A/C expression compared to control. Tight junction protein claudin-5 was also decreased under these conditions. ETA or ETB receptor blockade during infection did not affect ET-1 secretion or the expression of cell senescence markers. Current findings suggest that P. gingivalis infection may compromise endothelial integrity and activate the ET system.

Keywords: Porphyromonas gingivalis; cellules endothéliales; contributions vasculaires aux déficits cognitifs; endothelial cells; endothelin-1; endothéline-1; vascular contributions to cognitive impairment.

MeSH terms

  • Bacteroidaceae Infections* / metabolism
  • Base Composition
  • Brain / metabolism
  • Endothelial Cells* / metabolism
  • Endothelial Cells* / microbiology
  • Endothelin-1 / metabolism
  • Endothelins
  • Phylogeny
  • Porphyromonas gingivalis* / metabolism
  • RNA, Ribosomal, 16S
  • Receptor, Endothelin A / metabolism
  • Receptor, Endothelin B / metabolism
  • Receptors, Endothelin / metabolism
  • Sequence Analysis, DNA


  • Endothelin-1
  • Endothelins
  • RNA, Ribosomal, 16S
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Receptors, Endothelin