Background: Preeclampsia affects 2–8% of pregnancies and is a leading cause of maternal and fetal morbidity, mortality, and preterm birth worldwide[1]. It is characterised by impaired placental development arising from dysregulated trophoblast invasion and angiogenesis[2], driven in part by elevated circulating anti-angiogenic factors such as soluble endoglin (sEng). Transthyretin (TTR) is a transport protein involved in thyroid hormone distribution. We have previously shown that TTR can bind sEng and facilitate its hepatic uptake[3], suggesting a potential role in regulating sEng bioavailability.

Methods: In this study, we investigated whether TTR can attenuate the anti-angiogenic effects of sEng using a human umbilical vein endothelial cell (HUVEC) tube formation assay. HUVECs were seeded onto extracellular matrix-coated 96-well plates and treated with sEng (100 ng/mL) in the presence or absence of TTR (1 μM) for 4 hours at 37°C in 5% CO₂. Tube formation was imaged and quantified by measuring junction number, mesh formation, and total tube length.

Results: Treatment with sEng significantly impaired angiogenesis across all parameters. Co-treatment with TTR markedly rescued these effects, restoring endothelial network formation to levels comparable to controls. These findings support a functional interaction between TTR and sEng.

Conclusion: We propose that TTR binds sEng, limiting its bioavailability and reducing its interference with TGF-β signalling pathways that drive endothelial dysfunction. This mechanism suggests a potential protective role for TTR in preserving vascular function in preeclampsia and highlights a novel pathway for therapeutic investigation.

1. Burton, G.J. and E. Jauniaux, Proc Biol Sci, 2023. 290(1997): p. 20230191.
2. Chen, D.B. and J. Zheng, Microcirculation, 2014. 21(1): p. 15-25.
3. Young, M., et al. Mol Cell Endocrinol, 2023. 562: p. 111851.