Apolipoprotein A-I protects normal integration of the trophoblast into endothelial cellular networks in an <em>in vitro</em> model of Preeclampsia — ASN Events
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Apolipoprotein A-I protects normal integration of the trophoblast into endothelial cellular networks in an in vitro model of Preeclampsia (#220)

Francesca Charlton 1 , Bei Xu 1 2 , Angela Makris 1 3 4 , Kerry-Anne Rye 1 , Annemarie Hennessy 1 3 5
  1. The Heart Research Institute, Newtown, NSW, Australia
  2. School of Medicine, University of Western Sydney, Campbelltown, Sydney, NSW, Australia
  3. School of Medicine, University of Western Sydney, Campbelltown, Sydney, NSW, Australia
  4. Liverpool Hospital, Liverpool, Sydney, NSW, Australia
  5. Campbelltown Hospital, Campbelltown, Sydney, NSW, Australia

INTRODUCTION: Failure of the trophoblast to appropriately invade uterine spiral arteries is an initiating event in preeclampsia, a disorder characterised by hypertension and endothelial dysfunction. A dyslipidemia (low plasma levels of high density lipoproteins (HDL) and elevated triglycerides) has also been described in preeclampsia. The pro-inflammatory cytokine TNF-α inhibits trophoblast invasion of uterine endothelial cells. The effect of apoliopoprotein A-I, the main apolipoprotein component of HDL, on trophoblast incorporation into endothelial tubules ±TNF-α is investigated using the in vitro HTR-8/SVneo-Uterine endothelial cell (Tr-UEc) co-culture model.

OBJECTIVES: This study asks if apoA-I, which has established anti-inflammatory properties, can protect against the deleterious effect of TNF-α on trophoblast-endothelial cell interactions.

METHODS: The Tr-UEc co-culture model was used to investigate the effect of apoA-I on trophoblast incorporation into endothelial tubules ±TNF-α. UtMvEcs were pre-incubated with lipid free apoA-I (final apoA-I concentration 1mg/mL) for 16hrs prior to seeding onto matrigel. Tubules formed within 4hrs. Fluorescence-labelled HTR-8/SVneo trophoblast cells were then co-cultured with the endothelial cells ±TNF-α (final concentration of 0.2ng/mL). Live Cell Imaging techniques (Zeiss Axiovert) captured the integration in real time, bright field and fluorescent images were captured after 24hrs. The effect of TNF-α on trophoblast cell invasion was quantified with ImageJ software.

RESULTS: TNF-α inhibited trophoblast cell integration into endothelial tubular structures by 24.1±3.7% (p<0.001). This effect was reversed when the endothelial cells were pre-incubated for 16hrs with lipid free apoA-I (p<0.001 compared to non-incubated cells). Live cell images clearly demonstrate a disruption to the normal integration of trophoblast into endothelial tubular structures in the presence of TNF-α. The protective effect conferred by pre-incubation of endothelial cells with apoA-I against TNF-α is clearly visible.

CONCLUSION: apoA-I enhances trophoblast-endothelial cell integration in the presence of a pro-inflammatory stimulus. A healthy lipid profile may affect pregnancy outcomes by priming endothelial cells in preparation for trophoblast invasion.