Receptor for advanced glycation endproducts mediates pro-atherogenic responses to periodontal infection in vascular endothelial cells

Andreas Pollreisz, Barry I. Hudson, Jong S. Chang, Wu Qu, Bin Cheng, Panos N. Papapanou, Ann Marie Schmidt, Evanthia Lalla

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Objective: A link between periodontal infections and an increased risk for vascular disease has been demonstrated. Porphyromonas gingivalis, a major periodontal pathogen, localizes in human atherosclerotic plaques, accelerates atherosclerosis in animal models and modulates vascular cell function. The receptor for advanced glycation endproducts (RAGE) regulates vascular inflammation and atherogenesis. We hypothesized that RAGE is involved in P. gingivalis's contribution to pro-atherogenic responses in vascular endothelial cells. Methods and results: Murine aortic endothelial cells (MAEC) were isolated from wild-type C57BL/6 or RAGE-/- mice and were infected with P. gingivalis strain 381. P. gingivalis 381 infection significantly enhanced expression of RAGE in wild-type MAEC. Levels of pro-atherogenic advanced glycation endproducts (AGEs) and monocyte chemoattractant protein 1 (MCP-1) were significantly increased in wild-type MAEC following P. gingivalis 381 infection, but were unaffected in MAEC from RAGE-/- mice or in MAEC infected with DPG3, a fimbriae-deficient mutant of P. gingivalis 381. Consistent with a role for oxidative stress and an AGE-dependent activation of RAGE in this setting, both antioxidant treatment and AGE blockade significantly suppressed RAGE gene expression and RAGE and MCP-1 protein levels in P. gingivalis 381-infected human aortic endothelial cells (HAEC). Conclusion: The present findings implicate for the first time the AGE-RAGE axis in the amplification of pro-atherogenic responses triggered by P. gingivalis in vascular endothelial cells.

Original languageEnglish (US)
Pages (from-to)451-456
Number of pages6
JournalAtherosclerosis
Volume212
Issue number2
DOIs
StatePublished - Oct 2010
Externally publishedYes

Keywords

  • Atherosclerosis
  • Endothelial cells
  • Infection
  • P. gingivalis
  • Periodontitis
  • RAGE
  • Vascular inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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