K CHAU1,2, B XU1, A HENNESSY1,2,3, A MAKRIS1,4
1Heart Research Institute, Newtown, Australia, 2Sydney Medical School, University of Sydney, Sydney, Australia, 3School of Medicine, Western Sydney University , Campbelltown, Australia, 4The Renal Unit, Liverpool Hospital, Liverpool, Australia
Aim: To evaluate the effect of preventative treatment with low-dose aspirin (LDA) in a mouse model of experimental preeclampsia (EPE) induced by tumour necrosis factor-α (TNF-α) infusion.
Background: LDA is prescribed as a preventative treatment for women at risk of preeclampsia but its mechanism of action is uncertain. Treatment with LDA is effective when commenced prior to 16 weeks’ gestation suggesting a potential effect of LDA on placental development but this remains unproven.
Methods: Pregnant C57/BL6 mice were treated from gestational day (gd) 10 daily with oral LDA plus intraperitoneal 100 µL of phosphate buffered saline (PBS) or PBS only. Mice were allocated to one of 3 experimental arms: 1) Animals (n=5 per group) were euthanised on gd13 to assess the effect of LDA in early pregnancy; 2) Animals had continuous blood pressure (BP) measurement by intra-arterial radio-telemetry (n=5 per group) and had EPE induced by continuous TNF-α (500 ng/kg/day) infusion from gd13; 3) Animals (n=3 per group) had EPE induced as above and live placenta magnetic resonance imaging (MRI) in an 11.74 Tesla spectrometer on gd17. Animals in arms 2 and 3 were euthanized at gd17 and blood, urine and tissue samples were collected. Data was analysed with GraphPad Prism 7.
Results: LDA animals euthanised at gd13 demonstrated increased placenta PlGF (p=0.02) mRNA expression as compared with controls. In animals with EPE there was no difference in BP (p=1), proteinuria (p>0.9) or T2 labyrinthine/junctional zone ratio (p=1) at gd17 between control and LDA treated animals.
Conclusions: LDA administered in early pregnancy increases placenta PlGF mRNA expression but this does not influence the subsequent development of EPE features induced by TNF-α infusion.
Dr Katrina Chau is a renal physician at Blacktown Hospital and is completing a PhD in preeclampsia under the supervision of A/Prof Angela Makris and Prof Annemarie Hennessy.