Overview of extracellular vesicles in the pathogenesis of preeclampsia†

Abstract

Abstract Preeclampsia (PE) is a leading cause of maternal and fetal-neonatal deaths, and its pathogenesis has been linked to the involvement of extracellular vesicles (EVs). EVs are a heterogeneous group of cell-originated membranous vesicles including exosomes, microvesicles, and apoptotic bodies. EVs transport various bioactive cargos such as lipids, proteins, or nucleic acids, and thus mediate cellular communication and contribute to the proper functioning of cells, organs and processes, including normal pregnancy. Numerous studies have reported that EVs are associated with abnormal levels of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), and placental growth factor (PlGF) in PE. EVs isolated from preeclamptic women have been implicated in trophoblast dysfunction and have been reported to activate endothelium, monocytes, and platelets, and to be involved in defective placentation, imbalanced angiogenesis, and intravascular inflammation. When injected into pregnant rodents, these EVs induced hypertension, proteinuria, and adverse fetal outcomes. Deciphering the contribution of EVs to PE will advance our current understanding of this disorder and may lead to more clinical strategies for the management of PE. Of note, the composition of EV cargos may be characteristic of the status and stages of gestation, providing researchers the possibility of one day using EVs as novel, noninvasive, biomarkers for early screening of PE. Herein, we reviewed the latest research into EVs with emphasis on their role in the pathogenesis of PE and their applications as biomarkers in the early screening of this pregnancy-specific disorder. Graphical Abstract The role of extracellular vesicles in preeclampsia. Preeclampsia (PE) is a leading cause of maternal and neo-fetal death, and its pathogenesis has been linked to extracellular vesicles (EVs). EVs are a heterogeneous collection of cell-released, membrane-enclosed, and nano-sized particle that are categorized into apoptotic bodies (ABs), microvesicles (MVs), and exosomes (Exos). EVs are mainly derived from endothelial cells, platelets, trophoblasts, monocytes, T cells, and mesenchymal stem cells. EVs mediate communication among these donor cells via the transfer of their unique cargos. This communication is crucial for many body functions, including normal gestation. In subjects with PE, EVs not only change their counts but also exhibit altered molecular loads, which have been associated with PE-related risk factors and are reported to have pro-antiangiogenic, procoagulant, and pro-inflammatory effects. Several lines of evidence confirm that EVs are engaged in imbalanced angiogenesis, endothelial dysfunction and activation, and intravascular inflammation, all of which ultimately contribute to the development of this complex pregnancy-specific disorder. Deciphering the roles of EVs in women with PE will offer us useful perspectives to advance our understanding of this disease and may ultimately help to improve maternal and fetal outcomes.