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Human umbilical artery endothelial cells from Large-for-Gestational-Age newborn have increased antioxidant efficiency

Ivo Carrasco-Wong1, Cherie Hernández2, Carlos Jara-Gutiérrez3

  • 1Department of Cellular and Molecular Biology, Cell & Molecular Biology PhD Program, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.

Journal of Cellular Physiology
|April 3, 2019
PubMed

Insights

Maternal obesity leads to oxidative stress in newborns, altering fetal vascular cells. These cells develop a more efficient antioxidant system, potentially due to epigenetic changes from the intrauterine environment.

Area of Science:

  • Reproductive biology
  • Perinatal medicine
  • Cellular and molecular biology

Background:

  • Maternal obesity is a global health issue, affecting over a third of women of reproductive age.
  • Maternal obesity is linked to increased oxidative stress in mothers, placentas, and newborns, potentially causing vascular dysfunction in large-for-gestational-age (LGA) newborns.
  • The precise cellular and molecular mechanisms underlying this effect remain unclear.

Purpose of the Study:

  • To investigate the cellular and molecular mechanisms of oxidative stress in human umbilical artery endothelial cells (HUAEC) from LGA newborns.
  • To explore the alterations in the antioxidant system of LGA-HUAEC.

Main Methods:

  • Analysis of oxidative stress markers (O2-, GSH:GSSG ratio, NRF2 mRNA) in LGA-HUAEC.
  • Assessment of antioxidant enzyme expression (GPX1) and function (HyPer biosensor) under oxidative challenge.
  • Chromatin accessibility assay (DNase-HS) to investigate epigenetic modifications.

Main Results:

  • LGA-HUAEC exhibited higher O2- levels, superoxide dismutase activity, and heme oxygenase 1 mRNA, with a lower GSH:GSSG ratio and NRF2 mRNA levels.
  • LGA-HUAEC showed enhanced Glutathione Peroxidase 1 (GPX1) expression and a more efficient antioxidant response to hydrogen peroxide.
  • DNase-HS assay revealed an open chromatin state in the GPX1 promoter region of LGA-HUAEC, suggesting epigenetic regulation.

Conclusions:

  • LGA-HUAEC possess an altered cellular and molecular antioxidant system.
  • A chronic intrauterine pro-oxidant environment, associated with maternal obesity, may induce a more efficient fetal vascular cell antioxidant system.
  • This enhanced antioxidant capacity might be maintained postnatally through epigenetic mechanisms.

Keywords:
endothelial cellsepigeneticslarge-for-gestational-age (LGA)maternal obesityoxidative stress

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