Deep Sequencing Identified Dysregulated Circulating MicroRNAs in Late Onset Preeclampsia

Mavreli, Danai; Lykoudi, Alexandra; Lambrou, George Ι.; Papaioannou, George; Vrachnis, Nikolas; Kalantaridou, Sophia Ν.; Παπαντωνίου, Ν.; Kοlialexi, Aggeliki

doi:10.21873/invivo.12044

Cited by 17 publications

(22 citation statements)

References 36 publications

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“…If these processes are altered by changes in miRNA expression, critical parts of a healthy pregnancy could be compromised. Indeed, altered circulating miRNA profiles have been associated with several pregnancy complications, including preeclampsia, gestational diabetes, and preterm birth [22][23][24]. Evidence for the roles of exosomal miRNA during pregnancy, including evidence for miRNA effects in mouse models, has been reviewed by Yang et al, suggesting that miRNA is not simply a biomarker, but is also an active participant with many regulatory roles [25].…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicle-enriched miRNA profiles across pregnancy in the MADRES cohort

et al. 2021

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MicroRNA (miRNA) circulating in plasma have been proposed as biomarkers for a variety of conditions and diseases, including complications during pregnancy. During pregnancy, about 15–25% of maternal plasma exosomes, a small size-class of EVs, are hypothesized to originate in the placenta, and may play a role in communication between the fetus and mother. However, few studies have addressed changes in miRNA over the course of pregnancy with repeated measures, nor focused on diverse populations. We describe changes in miRNA in early and late pregnancy from the MADRES cohort of primarily low-income Hispanic women based in Los Angeles, CA. miRNA derived from extracellular-vesicles (EVs) were isolated from maternal blood plasma samples collected in early and late pregnancy. In this study, we identified 64 of 130 detectable miRNA which significantly increased with gestational age at the time of collection (GA), and 26 which decreased with GA. Possible fetal sex-specific associations were observed for 30 of these 90 significant miRNA. Predicted gene targets for miRNA significantly associated with GA were identified using MirDIP and were found to be enriched for Gene Ontology categories that included energetic and metabolic processes but were underrepresented in immune-related categories. Circulating EV-associated miRNA during pregnancy are likely important for maternal-fetal communication, and may play roles in supporting and maintaining a healthy pregnancy, given the changing needs of the fetus.

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Section: Introductionmentioning

confidence: 99%

Extracellular vesicle-enriched miRNA profiles across pregnancy in the MADRES cohort

et al. 2021

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“…Other studies focused more likely on the search of circulating microRNA biomarkers detectable in maternal plasma or serum with predictive value for PE and demonstrated a whole range of diverse microRNAs with altered expression during the first trimester of gestation in women subsequently developing PE involving miR-1233 (up-regulated), miR-520a (up-regulated), miR-210 (up-regulated), miR-144 (down-regulated) [ 25 ], miR-520g (up-regulated) [ 26 ], miR-942 (down-regulated) [ 27 ], miR-517-5p (up-regulated) [ 28 ], miR-423-5p (up-regulated) [ 29 ], miR-182 (down-regulated), miR-10b (down-regulated), miR-25 (down-regulated), miR-4433b (up-regulated), miR-99b (down-regulated), miR-143 (down-regulated), miR-151a (down-regulated), miR-191 (down-regulated), miR-146b (down-regulated), miR-221 (up-regulated), let-7g (up-regulated) [ 30 ], miR-23b-5p (down-regulated), miR-99b-5p (down-regulated) [ 31 ], and miR-125b (up-regulated) [ 32 ]. Nevertheless, it does not make sense to compare intracellular and extracellular microRNA expression profiles, since they can differ for various reasons.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Disease-Associated MicroRNA Dysregulation during the First Trimester of Gestation in Women with Chronic Hypertension and Normotensive Women Subsequently Developing Gestational Hypertension or Preeclampsia with or without Fetal Growth Restriction

2022

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The aim of the study was to assess if cardiovascular disease-associated microRNAs would be able to predict during the early stages of gestation (within 10 to 13 weeks) subsequent onset of hypertensive pregnancy-related complications: gestational hypertension (GH) or preeclampsia (PE). Secondly, the goal of the study was to assess if cardiovascular disease-associated microRNAs would be able to detect the presence of chronic hypertension in early pregnancies. The retrospective study was performed on whole peripheral blood samples collected from singleton Caucasian pregnancies within the period November 2012 to March 2020. The case control study, nested in a cohort, involved all women with chronic hypertension (n = 29), all normotensive women that later developed GH (n = 83) or PE with or without fetal growth restriction (FGR) (n = 66), and 80 controls selected on the base of equal sample storage time. Whole peripheral blood profiling was performed with the selection of 29 cardiovascular disease-associated microRNAs using real-time RT-PCR. Upregulation of miR-1-3p (51.72% at 10.0% FPR) was observed in patients with chronic hypertension only. Upregulation of miR-20a-5p (44.83% and 33.33% at 10.0% FPR) and miR-146a-5p (65.52% and 42.42% at 10.0% FPR) was observed in patients with chronic hypertension and normotensive women with later occurrence of PE. Upregulation of miR-181a-5p was detected in normotensive women subsequently developing GH (22.89% at 10.0% FPR) or PE (40.91% at 10.0% FPR). In a part of women with subsequent onset of PE, upregulation of miR-143-3p (24.24% at 10.0% FPR), miR-145-5p (21.21% at 10.0% FPR), and miR-574-3p (27.27% at 10.0% FPR) was also present. The combination of microRNA biomarkers (miR-20a-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, and miR-574-3p) can predict the later occurrence of PE in 48.48% of pregnancies at 10.0% FPR in early stages of gestation. The combination of upregulated microRNA biomarkers (miR-1-3p, miR-20a-5p, and miR-146a-5p) is able to identify 72.41% of pregnancies with chronic hypertension at 10.0% FPR in early stages of gestation. Cardiovascular disease-associated microRNAs represent promising biomarkers with very good diagnostical potential to be implemented into the current first trimester screening program to predict later occurrence of PE with or without FGR. The comparison of the predictive results of the routine first trimester screening for PE and/or FGR based on the criteria of the Fetal Medicine Foundation and the first trimester screening for PE wo/w FGR using a panel of six cardiovascular disease-associated microRNAs only revealed that the detection rate of PE increased 1.45-fold (48.48% vs. 33.33%).

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“…In earlyonset PE, miR-431, miR-518a-5p, and miR-124 were up-regulated in the placenta tissues (Lykoudi et al, 2018), and miR-423-5p was up-regulated in the circulating blood (Timofeeva et al, 2018), whereas miR-544 and miR-3942 were down-regulated in the placenta tissues (Lykoudi et al, 2018). In late-onset PE, miR-383 and miR-1183 were up-regulated in the placenta tissues (Lykoudi et al, 2018), whereas miR-23b-5p and miR-99b-5p were down-regulated in the circulating blood (Mavreli et al, 2020). However, the functional significance of these miRNAs in the pathogenesis of PE has not been confirmed and elucidated.…”

Section: Discussionmentioning

confidence: 99%

Recent Advances of MicroRNAs, Long Non-coding RNAs, and Circular RNAs in Preeclampsia

Chen

Shi-Wen

et al. 2021

Front. Physiol.

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Preeclampsia is a clinical syndrome characterized by multiple-organ dysfunction, such as maternal hypertension and proteinuria, after 20 weeks of gestation. It is a common cause of fetal growth restriction, fetal malformation, and maternal death. At present, termination of pregnancy is the only way to prevent the development of the disease. Non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, are involved in important pathological and physiological functions in life cycle activities including ontogeny, reproduction, apoptosis, and cell reprogramming, and are closely associated with human diseases. Accumulating evidence suggests that non-coding RNAs are involved in the pathogenesis of preeclampsia through regulation of various physiological functions. In this review, we discuss the current evidence of the pathogenesis of preeclampsia, introduce the types and biological functions of non-coding RNA, and summarize the roles of non-coding RNA in the pathophysiological development of preeclampsia from the perspectives of oxidative stress, hypoxia, angiogenesis, decidualization, trophoblast invasion and proliferation, immune regulation, and inflammation. Finally, we briefly discuss the potential clinical application and future prospects of non-coding RNA as a biomarker for the diagnosis of preeclampsia.

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Deep Sequencing Identified Dysregulated Circulating MicroRNAs in Late Onset Preeclampsia

Cited by 17 publications

References 36 publications

Extracellular vesicle-enriched miRNA profiles across pregnancy in the MADRES cohort

Extracellular vesicle-enriched miRNA profiles across pregnancy in the MADRES cohort

Cardiovascular Disease-Associated MicroRNA Dysregulation during the First Trimester of Gestation in Women with Chronic Hypertension and Normotensive Women Subsequently Developing Gestational Hypertension or Preeclampsia with or without Fetal Growth Restriction

Recent Advances of MicroRNAs, Long Non-coding RNAs, and Circular RNAs in Preeclampsia

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