Accumulation of Advanced Glycation End Products Involved in Inflammation and Contributing to Severe Preeclampsia, in Maternal Blood, Umbilical Blood and Placental Tissues

Gynecol Obstet Invest. 2017;82(4):388-397. doi: 10.1159/000448141. Epub 2016 Aug 10.

Abstract

Objective: To investigate the expression of advanced glycation end products (AGEs) and the receptor for AGE (RAGEs) in maternal blood, umbilical blood and placental tissues in women with severe preeclampsia (sPE) as well as any association with inflammatory processes.

Methods: The expressions of AGEs, RAGE, tumor necrosis factor-alpha (TNF)-α and vascular cell adhesion molecule-1 (VCAM)-1 in placental tissues were measured using immunohistochemistry. The levels of AGEs, RAGE, TNF-α and VCAM-1 in maternal blood, umbilical blood and placental extracts were assessed using enzyme-linked immunosorbent assays. Placental RAGE, TNF-α and VCAM-1 mRNA expression levels were determined by PCR. Placental AGEs, RAGE, TNF-α and VCAM-1 protein levels were determined by western blotting.

Results: The levels of AGEs, TNF-α and VCAM-1 in the maternal tissues and umbilical blood were significantly higher in the sPE group than in the normal pregnancy (NP) controls (p < 0.05). The serum level of sRAGE in the umbilical blood was lower in the sPE group than in the NP controls (p < 0.05), while sRAGE was higher in the maternal blood of sPE than in the NP (p < 0.05). The maternal serum levels of AGEs were positively correlated with that of TNF-α and VCAM-1 in the maternal blood. There were no correlations between the levels of RAGE, TNF-α or VCAM-1 in maternal blood or umbilical serum. There were no correlations between the levels of sRAGE and TNF-α or VCAM-1 in maternal blood or umbilical serum. The levels of AGEs were positively correlated with those of TNF-α and VCAM-1 in placental lysates.

Conclusion: AGEs and RAGE appear to act as important mediators in regulating the inflammatory pathways of preeclampsia.

Keywords: Advanced glycation end products; Preeclampsia; Receptor for advanced glycation end-products; Tumor necrosis factor-alpha; Vascular cell adhesion molecule-1.

MeSH terms

  • Adult
  • Blotting, Western
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fetal Blood / metabolism*
  • Glycation End Products, Advanced / metabolism*
  • Humans
  • Inflammation / metabolism
  • Placenta / metabolism
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / metabolism*
  • Pregnancy
  • Receptor for Advanced Glycation End Products / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Glycation End Products, Advanced
  • Receptor for Advanced Glycation End Products
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1