Extracellular vesicles in normal pregnancy and pregnancy‐related diseases

Zhang, Jiayin; Li, Haibo; Fan, Boyue; Xu, Wenrong; Zhang, Xu

doi:10.1111/jcmm.15144

Cited by 53 publications

(53 citation statements)

References 105 publications

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“…All eukaryotic cells are capable of secreting various types of membrane vesicles, known as extracellular vesicles (EVs), to carry or exchange a wide range of cargo involved in multiple physiological and pathological processes. In healthy pregnancy, these vesicles participate in many important physiological activities including embryo implantation, immune-modulation, spiral artery remodeling and metabolism adaptations (169).…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?

et al. 2020

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Placental insufficiency and adipose tissue dysregulation are postulated to play key roles in the pathophysiology of both pre-eclampsia (PE) and gestational diabetes mellitus (GDM). A dysfunctional release of deleterious signaling motifs can offset an increase in circulating oxidative stressors, pro-inflammatory factors and various cytokines. It has been previously postulated that endothelial dysfunction, instigated by signaling from endocrine organs such as the placenta and adipose tissue, may be a key mediator of the vasculopathy that is evident in both adverse obstetric complications. These signaling pathways also have significant effects on long term maternal cardiometabolic health outcomes, specifically cardiovascular disease, hypertension, and type II diabetes. Recent studies have noted that both PE and GDM are strongly associated with lower maternal flow-mediated dilation, however the exact pathways which link endothelial dysfunction to clinical outcomes in these complications remains in question. The current diagnostic regimen for both PE and GDM lacks specificity and consistency in relation to clinical guidelines. Furthermore, current therapeutic options rely largely on clinical symptom control such as antihypertensives and insulin therapy, rather than that of early intervention or prophylaxis. A better understanding of the pathogenic origin of these obstetric complications will allow for more targeted therapeutic interventions. In this review we will explore the complex signaling relationship between the placenta and adipose tissue in PE and GDM and investigate how these intricate pathways affect maternal endothelial function and, hence, play a role in acute pathophysiology and the development of future chronic maternal health outcomes.

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Section: Extracellular Vesiclesmentioning

confidence: 99%

Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?

et al. 2020

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“…The physiological release of EVs is usually increased during pregnancy, and EVs have been shown to carry or express increased levels of proinflammatory and procoagulant molecules on their surface, which contribute to an enhanced inflammation and hypercoagulation state significant for pregnancy [ 10 ]. However, there are several studies suggesting that elevated concentrations and altered profiles of EVs play a role in pregnancy disorders, such as preeclampsia (PE), gestational diabetes mellitus (GDM), recurrent fetal loss, and preterm birth [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles and Antiphospholipid Syndrome: State-of-the-Art and Future Challenges

Štok

Čučnik

Sodin‐Šemrl

et al. 2021

IJMS

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Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thromboembolism, obstetric complications, and the presence of antiphospholipid antibodies (aPL). Extracellular vesicles (EVs) play a key role in intercellular communication and connectivity and are known to be involved in endothelial and vascular pathologies. Despite well-characterized in vitro and in vivo models of APS pathology, the field of EVs remains largely unexplored. This review recapitulates recent findings on the role of EVs in APS, focusing on their contribution to endothelial dysfunction. Several studies have found that APS patients with a history of thrombotic events have increased levels of EVs, particularly of endothelial origin. In obstetric APS, research on plasma levels of EVs is limited, but it appears that levels of EVs are increased. In general, there is evidence that EVs activate endothelial cells, exhibit proinflammatory and procoagulant effects, interact directly with cell receptors, and transfer biological material. Future studies on EVs in APS may provide new insights into APS pathology and reveal their potential as biomarkers to identify patients at increased risk.

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“…A total of 62 proteins qualified for diagnosis from 132 proteins evaluated through ROC analysis, of which a group of three exosomal proteins, namely alpha-2-macroglobulin (α2M), human endogenous medium-reiteration-frequency-family-34 ORF (HEMO), and mannose binding lectin 2 (MBL2), displayed a specificity of 83% with median AUC of 0.89. This group, if validated, would enable the stratification of patients which are subject to a high risk of spontaneous PTB before clinical symptoms appear [ 241 ].…”

Section: Preterm Birthmentioning

confidence: 99%

“…Another study conducted by Rodosthenous et al reported higher expression levels of miR-942-5p, miR-223-5p, miR-20b-5p, miR-324-3p, and miR127-3p in second trimester patients that later gave birth to SGA infants. Of these, miR-127-3p was also linked to abnormal fetal growth [ 241 , 248 ].…”

Section: Fetal Growth Restrictionmentioning

confidence: 99%

Pregnancy-Related Extracellular Vesicles Revisited

Condrat

Varlas

Duica

et al. 2021

IJMS

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Extracellular vesicles (EVs) are small vesicles ranging from 20–200 nm to 10 μm in diameter that are discharged and taken in by many different types of cells. Depending on the nature and quantity of their content—which generally includes proteins, lipids as well as microRNAs (miRNAs), messenger-RNA (mRNA), and DNA—these particles can bring about functional modifications in the receiving cells. During pregnancy, placenta and/or fetal-derived EVs have recently been isolated, eliciting interest in discovering their clinical significance. To date, various studies have associated variations in the circulating levels of maternal and fetal EVs and their contents, with complications including gestational diabetes and preeclampsia, ultimately leading to adverse pregnancy outcomes. Furthermore, EVs have also been identified as messengers and important players in viral infections during pregnancy, as well as in various congenital malformations. Their presence can be detected in the maternal blood from the first trimester and their level increases towards term, thus acting as liquid biopsies that give invaluable insight into the status of the feto-placental unit. However, their exact roles in the metabolic and vascular adaptations associated with physiological and pathological pregnancy is still under investigation. Analyzing peer-reviewed journal articles available in online databases, the purpose of this review is to synthesize current knowledge regarding the utility of quantification of pregnancy related EVs in general and placental EVs in particular as non-invasive evidence of placental dysfunction and adverse pregnancy outcomes, and to develop the current understanding of these particles and their applicability in clinical practice.

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Extracellular vesicles in normal pregnancy and pregnancy‐related diseases

Cited by 53 publications

References 105 publications

Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?

Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?

Extracellular Vesicles and Antiphospholipid Syndrome: State-of-the-Art and Future Challenges

Pregnancy-Related Extracellular Vesicles Revisited

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