Missing links in preeclampsia cell model systems of endothelial dysfunction

• Published in: Trends in molecular medicine Vol. 29; no. 7; pp. 541 - 553
• Main Authors: Viana-Mattioli, Sarah, Fonseca-Alaniz, Miriam Helena, Pinheiro-de-Sousa, Iguaracy, Krieger, José Eduardo, Sandrim, Valéria Cristina
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2023
• Subjects: Endothelial Cells; endothelial dysfunction; Female; Humans; Hypertension; Ischemia; omics; Placenta; Pre-Eclampsia - etiology; preeclampsia; Pregnancy; shear stress; shear stress; preeclampsia; omics; endothelial dysfunction
• ISSN: 1471-4914; 1471-499X
• DOI: 10.1016/j.molmed.2023.04.003

Systemic endothelial dysfunction holds particular relevance in the context of preeclampsia because it has been associated with circulating placental factors, maternal major symptoms, and later cardiovascular risk.Studies profiling changes in preeclamptic maternal endothelial function have been explored for a long time but in vivo and in vitro models both have several limitations.Shear stress is a hemodynamic force that strongly regulates endothelial function and dysfunction. This biomechanical force is not considered by the majority of in vitro studies on this topic because they mostly utilize static endothelial cell cultures.The combination of advances in biotechnology and biomolecular approaches can improve our knowledge of the missing links between circulating biomarkers and maternal endothelial dysfunction in preeclampsia. This will provide a better understanding of its pathophysiology and lead to the identification of potential therapeutic targets. Preeclampsia, one of the main hypertensive disorders of pregnancy, is associated with circulating factors released by the ischemic placenta accompanied by systemic endothelial dysfunction. The etiology of preeclampsia remains poorly understood although it is associated with high maternal and fetal mortality and increased cardiovascular disease risk. Most cell model systems used for studying endothelial dysfunction have not taken into account hemodynamic physical factors such as shear-stress forces which may prevent extrapolation of cell data to in vivo settings. We overview the role of hemodynamic forces in modulating endothelial cell function and discuss strategies to reproduce this biological characteristic in vitro to improve our understanding of endothelial dysfunction associated with preeclampsia.