Angiogenic Imbalance Models of Preeclampsia: From Mechanisms to Clinics

Preeclampsia is a pregnancy-specific hypertensive disorder, clinically defined by new-onset hypertension with proteinuria or other maternal organ dysfunction. It is a leading cause of maternal and perinatal mortality worldwide and remains an incurable condition, with delivery as the only definitive treatment. The disorder originates in placental dysfunction, characterized by inadequate trophoblast invasion and impaired spiral uterine artery remodeling, resulting in syncytiotrophoblast stress and the release of placenta-derived factors. Increased placental secretion of antiangiogenic factors, including soluble fms-like tyrosine kinase-1 and soluble endoglin, promotes angiogenic imbalance and drives widespread maternal endothelial dysfunction. This narrative review synthesizes findings from human studies and experimental research models used to investigate angiogenic dysregulation in preeclampsia, with particular focus on in vitro and in vivo models, and emerging 3-dimensional placental platforms. In vitro models, such as trophoblast organoids, placenta-on-a-chip devices, and 3-dimensional bioprinted constructs, recapitulate key aspects of the placental microenvironment and enable detailed study of aberrant angiogenesis and how to target it, while reducing reliance on limited primary tissue and improving experimental control. Complementing in vitro models, in vivo models are essential for linking placenta-derived angiogenic imbalance to maternal disease phenotypes, therapeutic responses, and fetal outcomes. This review provides a comprehensive assessment of current literature on models that recapitulate angiogenic imbalance in preeclampsia. We emphasize the importance of integrating bioengineering, cell biology, and clinical insights to improve our understanding of preeclampsia pathogenesis and to develop predictive tools and therapeutic strategies to manage angiogenic dysregulation in preeclampsia.