LpPLA2 in GDM – a protective system for placenta and fetus?

PI Christian Wadsack

Aim: Gestational Diabetes Mellitus (GDM) and obesity are pregnancy conditions not only associated with low-grade inflammation, but also with oxidative stress in the placenta and fetus alike. In order to protect the feto-placental unit, anti-oxidative defense systems may have evolved. Placental macrophages (HBCs) may contribute to these systems. Lipoprotein-associated phospholipase A2 (LpPLA2) is an enzyme with unique substrate preference towards oxidized phospholipids (oxPL).

Whether cleavage of oxPL by LpPLA2 results in inflammation is currently under discussion. Here we tested the hypothesis: LpPLA2 is secreted by HBCs, acts in the fetal circulation and is regulated by the inflammatory environment of the mother.

Methods: LDL and HDL were isolated from cord blood plasma, LpPLA2 activity, ELISAs assessing oxidative stress and protein modifications were determined. LpPLA2 mass/activity was measured in HBC supernatant in control/diabetic cells and subsequently used in a Multiplex approach to identify cytokines.

Results: In contrast to adults, LpPLA2 activity was higher on fetal HDL than on LDL. Fetal plasma LpPLA2 activity was increased by GDM, HDL-LpPLA2 positive correlated with fetal cord blood insulin. HBCs showed an increase in LpPLA2 protein/activity upon insulin treatment, glucose had no effect. In placental tissue LpPLA2 was found to be significantly elevated in GDM, this increase was paralleled by an increase in PAFR expression.

Conclusions: LpPLA2 -upregulation by oxPL may represent a positive feedback loop. Maternal low grade pro-inflammatory conditions, i.e. GDM are associated with increased LpPLA2 activity in HBCs and offspring. We speculate that LpPLA2 represents an anti-oxidative defense system for placenta and fetus.


  • LpPLA2 can be regulated by pro- and anti-inflammatory stimuli within the diabetic/obese environment

  • HDL-associated LpPLA2 might exert anti-oxidative, athero-protective function in placenta and fetus