The Blocking of Integrin-Mediated Interactions with Maternal Endothelial Cells Reversed the Endothelial Cell Dysfunction Induced by EVs, Derived from Preeclamptic Placentae

Yan, Feng; Chen, Qi; Lau, Sandy; Tsai, Bridget W.; Groom, Katie; Barrett, Carolyn J.; Chamley, Larry

doi:10.3390/ijms232113115

Cited by 9 publications

(8 citation statements)

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“…These extracellular vesicles are enriched in anti-angiogenic factors, apoptosis-inducing ligands and active caspase 3, especially in early-onset pre-eclampsia 192,193 . Emerging evidence suggests that syncytiotrophoblast-released extracellular vesicles are internalized by endothelial cells, into which they release these factors and drive the maternal endothelial dysfunction and inflammation observed in pre-eclampsia 176,[194][195][196] .…”

Section: Dysregulated Placental Release Of Factorsmentioning

confidence: 99%

Pre-eclampsia

Dimitriadis

Rolnik

Zhou

et al. 2023

Nat Rev Dis Primers

265

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Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive pre-eclampsia have reduced life expectancy, with increased risks of stroke, cardiovascular disease and diabetes, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death and neurodevelopmental disability and cardiovascular and metabolic disease later in life. Preeclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (>20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. Pre-eclampsia is found only when a placenta is or was recently present and is classified as preterm (delivery <37 weeks of gestation), term (delivery ≥37 weeks of gestation) and postpartum pre-eclampsia. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. Available treatments target maternal hypertension and seizures, but the only 'cure' for pre-eclampsia is delivery of the dysfunctional placenta and baby, often prematurely. Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. Significant advances have been made in the prediction and prevention of preterm pre-eclampsia, which is predicted in early pregnancy through combined screening and is prevented with daily low-dose aspirin, starting before 16 weeks of gestation. By contrast, the prediction of term and postpartum pre-eclampsia is limited and there are no preventive treatments. Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new Nature Reviews Disease Primers | (2023) 9:8 2 0123456789();: Primer Epidemiology Incidence and mortalityThe global prevalence of all pre-eclampsia in the years 2002-2010 was estimated at 4.6% of deliveries but reported regional rates varied between 1% and 5.6% 14 . Where reported, the prevalence of preterm pre-eclampsia is <1% [15][16][17][18] . The prevalence of pre-eclampsia is generally reported as lower in low-income and middle-income countries (LMICs) (except sub-Saharan Africa) than in high-income countries (HICs) 19,20 ; however, it is likely that differences in classification, access to prenatal care and under-reporting in LMICs affect prevalence data 20,21 . Furthermore, most pre-eclampsia research is performed in HICs, potentially leading to bias and generalizability concerns in the populations sampled and the research questions asked.Hypertensive disorders of pregnancy (including pre-eclampsia) are the second most common cause (behind haemorrhage) of maternal Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rights...

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Section: Dysregulated Placental Release Of Factorsmentioning

confidence: 99%

Pre-eclampsia

Dimitriadis

Rolnik

Zhou

et al. 2023

Nat Rev Dis Primers

265

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“…To confirm that the EVs were derived from the syncytiotrophoblast, lysates of the micro‐EVs were demonstrated to contain cytokeratin a trophoblast marker (Figure S1d). Previously we have shown that micro‐EVs produced using this method are cytokeratin and CD63 positive but vimentin and calnexin negative and we have reported the proteome of these EVs 16,17 …”

Section: Resultsmentioning

confidence: 83%

“…To account for vesicles present in the FBS in media, we performed a negative control. For this, an equal volume of media was incubated with CMTPX dye at the concentration of 2.5 ng/mL in a 12‐well plate but without placental explants as published 16 . These FBS‐derived EVs will be referred to as EV vehicle control.…”

Section: Methodsmentioning

confidence: 99%

The interaction of placental micro‐EVs with immune cells in vivo and in vitro

Paek,

Brooks,

Graham

et al. 2023

American J Rep Immunol

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ProblemConsiderable evidence suggests that placental extracellular vesicles (EVs) interact with most types of leukocytes in vitro but in vivo biodistribution studies question whether these interactions are reflective of the situation in vivo.Method of StudyCellTracker Red CMTPX stained human placental micro‐EVs were isolated from first trimester placental explant cultures. Equivalent amounts of micro‐EVs were cultured with murine leukocytes in vitro or injected into pregnant or non‐pregnant mice. After intravenous injection, on day 12.5 of gestation, major organs and blood samples were harvested 30 min or 24 h post injection.ResultsWe screened cryosections of the organs and confirmed that human placental EVs were specifically localised to the spleen, liver and the lungs 30 min or 24 h after injection. Immunohistochemistry showed that most of the EVs interacted with macrophages in those three organs and some of them also associated with T and B lymphocytes in the spleen or endothelial cells in the lungs and liver. Flow cytometry demonstrated that there was very little interaction between circulating leukocytes and EVs in vivo. While minimal, significantly more EVs interacted with leukocytes in pregnant than nonpregnant mice.ConclusionThe major interaction between human placental micro‐EVs and maternal leukocytes appear to be with macrophages predominantly in the splenic marginal zone, liver and lungs with little interaction between EVs and circulating leukocytes. Since marginal zone macrophages induce tolerance after phagocytosing apoptotic bodies it is likely that phagocytosis of placental EVs by marginal zone macrophages may also contribute to maternal immune tolerance.

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“…There is currently no consensus on the preferred uptake mechanism of specific EVs (Mathieu et al, 2019 ). This is specifically relevant during pregnancy, as the pathways of placental EV uptake in maternal organs are still underexplored (Cronqvist et al, 2020 ; Li et al, 2020 ; Feng et al, 2022 ). Also, placental EV uptake seems to be an energy- and size-dependent process with decreased uptake rates at low temperatures and slower uptake of large EVs, which might affect EV-mediated signaling in placental pathophysiologies (Feng et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The ‘communicatome’ of pregnancy: spotlight on cellular and extravesicular chimerism

Graf,

Urbschat,

Arck

2024

EMBO Mol Med

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Communication via biological mediators between mother and fetus are key to reproductive success and offspring’s future health. The repertoire of mediators coding signals between mother and fetus is broad and includes soluble factors, membrane-bound particles and immune as well as non-immune cells. Based on the emergence of technological advancements over the last years, considerable progress has been made toward deciphering the “communicatome” between fetus and mother during pregnancy and even after birth. In this context, pregnancy-associated chimerism has sparked the attention among immunologists, since chimeric cells—although low in number—are maintained in the allogeneic host (mother or fetus) for years after birth. Other non-cellular structures of chimerism, e.g. extracellular vesicles (EVs), are increasingly recognized as modulators of pregnancy outcome and offspring’s health. We here discuss the origin, distribution and function of pregnancy-acquired microchimerism and chimeric EVs in mother and offspring. We also highlight the pioneering concept of maternal microchimeric cell-derived EVs in offspring. Such insights expand the understanding of pregnancy-associated health or disease risks in mother and offspring.

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The Blocking of Integrin-Mediated Interactions with Maternal Endothelial Cells Reversed the Endothelial Cell Dysfunction Induced by EVs, Derived from Preeclamptic Placentae

Cited by 9 publications

References 53 publications

Pre-eclampsia

Pre-eclampsia

The interaction of placental micro‐EVs with immune cells in vivo and in vitro

The ‘communicatome’ of pregnancy: spotlight on cellular and extravesicular chimerism

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