Placental extracellular vesicles and pre‐eclampsia

Abstract

Pre‐eclampsia is a hypertensive disease of pregnancy characterized by new‐onset hypertension, with either proteinuria and/or organ dysfunction. Pre‐eclampsia is a leading cause of maternal morbidity and mortality; however, the underlying cellular and molecular mechanisms are not well understood. There is consensus that the underlying mechanism(s) resulting in pre‐eclampsia is centered around abnormal placentation, inadequate spiral‐artery remodeling, and deficiency in trophoblast invasion, resulting in impaired maternal blood flow to the placenta and a release of signals and/or inflammatory mediators into maternal circulation triggering the systemic manifestations of pre‐eclampsia. ER stress, resulting in impaired autophagy and placental release of aggregated proteins, may also confer systemic stress to maternal organs in pre‐eclampsia. Extracellular vesicles (EVs), lipid‐bilayer enclosed structures containing macromolecules including proteins, miRNA, and other important nucleotides, have been suggested to play an important role in this maternal‐fetal communication. Circulating EVs are present in greater quantity in the plasma of pre‐eclampsia subjects compared to normal pregnancy, and the placental derived EVs have been shown to have altered protein and RNA cargo. In this review, we will focus on EVs and their role in pre‐eclampsia, specifically their role in immune responses, inflammation, altered angiogenesis, and endothelial dysfunction.

Planned Pregnancy in Kidney Transplantation. A Calculated Risk

“…Today, preeclampsia is considered a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. Underlying mechanism(s) include heme oxygenase and hydrogen sulfide pathways, autoantibodies, misfolded proteins, nitric oxide, oxidative stress, extracellular vesicles containing miRNA, and other important nucleotides [42,43]. These mechanisms can result in abnormal placentation, inadequate spiral artery remodeling, deficiency in trophoblast invasion, reduced maternal blood flow to the placenta, and a release of signals and/or inflammatory mediators into maternal circulation, triggering the systemic manifestations of preeclampsia.…”

Introduction to the special issue on extracellular vesicles and reproduction

“…In this Special Issue, our authors describe the nature of EVs and ways to isolate 24 and characterize 25 them, the importance of EVs in embryo‐endometrium cross‐talk, 26 the role of EVs in the male reproductive tract, 27 and the interactions of EVs with immune cells in pregnancy, 28 as well as the role of EVs in complicated pregnancies including preeclampsia, 29 antiphospholipid antibody syndrome, 30 gestational diabetes, 31 viral infections, 32 and preterm birth 33 . Extracellular vesicles continue to be important after pregnancy and their importance in milk is described 34 , as well as the potential usefulness of engineered EVs as vehicles for delivery of drugs or other desired cargos 34,35 …”

Etiological Value of Sterile Inflammation in Preeclampsia: Is It a Non-Infectious Pregnancy Complication?

“…Increased levels of DAMPs and their receptors such as TLR 4 have been detected in the PE placenta (Abrahams et al, 2005). Recently, extracellular vesicles have been recognized as an important carrier of protein aggregates, miRNA, mRNA, lipids and apoptotic factors that may mediate inflammatory responses associated with PE pathophysiology (Schuster et al, 2021). Circulating extracellular vesicles exist in greater quantity in the plasma of PE subjects vs. normal pregnancy (Gilani et al, 2016;Tong et al, 2017;Schuster et al, 2021;Tong et al, 2021).…”