Role of Extracellular Vesicles and microRNAs on Dysfunctional Angiogenesis during Preeclamptic Pregnancies

Abstract

Preeclampsia is a syndrome characterized by hypertension during pregnancy, which is a leading cause of morbidity and mortality in both mother and newborn in developing countries. Some advances have increased the understanding of pathophysiology of this disease. For example, reduced utero-placental blood flow associated with impaired trophoblast invasion may lead to a hypoxic placenta that releases harmful materials into the maternal and feto-placental circulation and impairs endothelial function. Identification of these harmful materials is one of the hot topics in the literature, since these provide potential biomarkers. Certainty, such knowledge will help us to understand the miscommunication between mother and fetus. In this review we highlight how placental extracellular vesicles and their cargo, such as small RNAs (i.e., microRNAs), might be involved in endothelial dysfunction, and then in the angiogenesis process, during preeclampsia. Currently only a few reports have addressed the potential role of endothelial regulatory miRNA in the impaired angiogenesis in preeclampsia. One of the main limitations in this area is the variability of the analyses performed in the current literature. This includes variability in the size of the particles analyzed, and broad variation in the exosomes considered. The quantity of microRNA targets genes suggest that practically all endothelial cell metabolic functions might be impaired. More studies are required to investigate mechanisms underlying miRNA released from placenta upon endothelial function involved in the angiogenenic process.

Isolation of human trophoblastic extracellular vesicles and characterization of their cargo and antiviral activity

“…Interestingly, our data point to the presence of hnRNP family members such as hnRNPA2B1 and hnRNPD within trophoblastic EVs and thus suggest that they play a role in miRNA packaging in PHT cells [74]. Lastly, the similar repertoire of miRNA in PHT cells and EVs suggests that trophoblastic EVs, which shield miRNA against degradation [75,76], are better than total plasma or protein-bound plasma miRNA for monitoring trophoblastic miRNA in health and disease [34–36,77,78]. …”

Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers

“…Interestingly, miR-210, one of the most expressed placental miRNAs, strongly linked with the hypoxia pathway, is vehiculated within placental EVs [263]. This miRNA participates in the EMT, vasculo/angiogenesis and cell migration, and could contribute to maternal endothelial dysfunction, a condition linked to eclampsia, a life-threatening emergency in pregnancy.…”

Extracellular vesicles and their immunomodulatory functions in pregnancy

“…Extracellular cues like hypoxia and glucose content have significant impact on biosynthesis of EVs including exosome (reviewed in [24]). Low oxygen concentrations increase the release of EVs from trophoblast cells with alterations in the bioactivity such as heightened release of inflammatory cytokines, namely TNF-α and IL-6 as well as dampening the cell migratory properties [48,96].…”