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Pregnancy Hypertens. 2012 Jul;2(3):198-9. doi: 10.1016/j.preghy.2012.04.042. Epub 2012 Jun 13.

OS041. Apolipoprotein A-I protects normal integration of the trophoblast into endothelial cellular networks in an in vitro model of preeclampsia.

Author information

1
Vasular Immunology Research Group, University of Western Sydney, Campbelltown, Sydney, Australia; Lipid Research Group, The Heart Research Institute, University of Western Sydney, Campbelltown, Sydney, Australia.
2
Vasular Immunology Research Group, University of Western Sydney, Campbelltown, Sydney, Australia; School of Medicine, University of Western Sydney, Campbelltown, Sydney, Australia.
3
Vasular Immunology Research Group, University of Western Sydney, Campbelltown, Sydney, Australia; School of Medicine, University of Western Sydney, Campbelltown, Sydney, Australia; Renal Unit, Liverpool Hospital, Liverpool, Australia.
4
Vasular Immunology Research Group, University of Western Sydney, Campbelltown, Sydney, Australia; School of Medicine, University of Western Sydney, Campbelltown, Sydney, Australia; Campbelltown Hospital, Campbelltown, Sydney, Australia.
5
Lipid Research Group, The Heart Research Institute, University of Western Sydney, Campbelltown, Sydney, Australia.

Abstract

INTRODUCTION:

Failure of the trophoblast to appropriately invade uterine spiral arteries is thought to be an initiating event in preeclampsia, a disorder associated with endothelial dysfunction. A dyslipidemia characterised by 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. Previous work using an in vitro JEG-3 cell/Uterine endothelial cell co-culture model investigated the effect of apoliopoprotein A-I, the main apolipoprotein component of HDL, on trophoblast incorporation into endothelial tubules in the presence and absence of TNF-α. These effects are now investigated using the human invasive trophoblast cell line HTR-8/SVneo.

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 in vitro trophoblast-uterine endothelial cell co-culture model was used to investigate the effect of apoA-I on trophoblast incorporation into endothelial tubules in the presence and absence of TNF-α. Uterine endothelial cells were pre-incubated with lipid free apoA-I (final apoA-I concentration 1 mg/mL) for 16h prior to seeding on matrigel coated plates. Tubules formed within 4h. Fluorescence-labelled HTR-8/SVneo trophoblast cells were then co-cultured with the endothelial cells±TNF-α (final concentration of 0.2ng/mL). Bright field and fluorescent images were captured after 24h. The effect of TNF-α on HTR-8/SVneo cell invasion was quantified with Image J software. Integration of HTR-8/SVneo trophoblast cells into uterine endothelial tubular networks was also imaged using live cell imaging techniques (Zeiss Axiovert).

RESULTS:

TNF-α inhibited HTR-8/SVneo (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 16h with lipid free apoA-I (p<0.001 compared to non-incubated cells). Live cell images of the co-culture 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 also clearly visible.

CONCLUSION:

Apolipoprotein A-I has been shown to enhance 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.

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