Background: Preeclampsia is a cardiovascular disorder diagnosed post 20 weeks’ of gestation. It is the leading cause of morbidity and mortality in pregnancy. Inappropriate placental development and growth due to aberrant angiogenesis and inflammation are the root causes of preeclampsia. However, due to ethical limitations and inadequacy of preeclampsia models, the molecular mechanisms regulating these processes are poorly understood. In this study, we investigated the role of important vascular and inflammatory proteins, FKBPL and Gal-3, in preeclampsia using human plasma/placental samples and new 3D microfluidics model of placental tissue.
Methods: ELISA or Western blotting were utilised to determine FKBPL and Gal-3 concentrations/expression in plasma (n=17 controls; n=30 preeclampsia) or placental samples (n≥6 per group). Human umbilical vein endothelial cell (HUVEC) vascular formation, and remodelling by trophoblast cells (ACH-3Ps), were characterised using 3D microfluidics chips, exposed to inflammatory tumour necrosis factor (TNF)-α. Immunofluorescent staining, Western blotting and ELISA were used to determine the secretion/expression of FKBPL and Gal-3 in the 3D microfluidics placental model.
Results and discussion: FKBPL and Gal-3 protein levels were upregulated in plasma (FKBPL; p<0.0001, Gal-3; p<0.05) and placental (FKBPL; p<0.05, Gal-3; p<0.05) preeclampsia samples compared to controls. Inflammation in 3D vascularised microfluidics placental models also led to an increase in FKBPL and Gal-3 protein expressions (FKBPL; p<0.05, Gal-3; p<0.05), in conjunction with changes in vascular pattern (branching pattern) and reduced vasculo-genesis potential (CD31; p<0.005).
Conclusions: The 3D human placenta microfluidic model can recapitulate human preeclampsia demonstrating upregulation of FKBPL and Gal-3, which is indicative of restricted angiogenesis with potentially a key role in inappropriate placental development and vascular dysfunction in preeclampsia