Angiogenic Properties of Placenta-Derived Extracellular Vesicles in Normal Pregnancy and in Preeclampsia.
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ABSTRACT:
SUBMITTER: Gebara N
PROVIDER: S-EPMC8160914 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To investigate the differentially expressed lncRNAs and mRNAs in human placenta between normal pregnancy and preeclampsia, we performed the human LncRNA microarray analysis of 8 samples from clinical patients.
2020-11-06 | GSE160888 | GEO
Project description:ObjectThis study aimed to investigate the diagnostic value of placenta-derived macrophage-stimulating protein ?-chain (MSP-?) before the 20th week of gestation for the early diagnosis of preeclampsia (PE).Methods and materialsTwo parts of this nested case-control study were simultaneously executed, and 1500 pregnant women were recruited. A total of 124 pregnant women were included in the plasma analysis part of this study. The MSP-? plasma level was measured before the 20th week of gestation, and the participants were followed until delivery. A case group of 62 women with PE and a control group of 62 women matched by gestational age, maternal age, and pre-pregnancy BMI (with normotensive pregnancies) were evaluated. In the placenta analysis part of this nested case-control study, the placentas of 34 pregnant women were randomly obtained. The placental levels of MSP were measured in 17 individuals with PE (case group) and in 17 women with a normotensive pregnancy matched by gestational age and maternal age (control group).ResultsThe plasma level of MSP-? was higher in the PE group than in the control group before the 20th week of gestation (p < 0.001). In addition, compared to the women with severe features in the PE group, those without severe features had a significantly higher plasma MSP-? level before the 20th week of gestation (p < 0.001). The area under the receiver operating characteristic curve (AUC) of MSP-? before the 20th week of gestation was 0.905 (95% CI, 0.811-0.962) for the women with early-onset PE without severe features. With regard to the placenta, the PE group (accumulated optical density, IOD [SUM] = 8862.37 ± 2064.42) exhibited increased MSP staining (more intense MSP staining or more extensive staining) compared with the control group (normal pregnancies (IOD [SUM] = 447.92 ± 114.72, P < 0.001). Furthermore, increased MSP staining was detected among the women without severe features compared with those with severe features in the PE group (IOD [SUM]: 12192.65 ± 5325.56 vs. 4104.83 ± 2383.06, P = 0.021).ConclusionAccording to the findings of this study, the plasma level of MSP-? may be associated with PE, and MSP-? may be considered a candidate protein for further analysis in studies of PE. Multicenter studies with larger sample sizes must be performed in the future to obtain accurate results regarding the predictive value of MSP-? in combination with other protein factors for the early diagnosis of PE.
| S-EPMC4999075 | biostudies-literature
Project description:Cardiosphere-derived cells mediate therapeutic regeneration in patients after myocardial infarction and are undergoing further clinical testing for cardiomyopathy. The beneficial effects of cardiosphere-derived cells are mediated by the secretion of exosomes and possibly other extracellular membrane vesicles (EMVs).This study sought to investigate the effect of cardiosphere-derived EMVs (CSp-EMVs) on fibroblasts in vitro and tested whether priming with CSp-EMVs could confer salutary properties on fibroblasts in vivo.CSp-EMVs were isolated from serum-free media conditioned for 3 days by cardiospheres. Dermal fibroblasts were primed with CSp-EMVs for 24 h followed by exosomal micro-ribonucleic acid profiling. In vivo, we injected CSp-EMV-primed or -unprimed dermal fibroblasts (or CSp-EMVs) in a chronic rat model of myocardial infarction and defined the functional and structural consequences.CSp-EMVs amplified their own biological signals: exposure of "inert" fibroblasts to CSp-EMVs rendered the fibroblasts therapeutic. Intramyocardially injected CSp-EMV-primed (but not unprimed) fibroblasts increased global pump function and vessel density while reducing scar mass. CSp-EMV priming caused fibroblasts to secrete much higher levels of stromal-cell-derived factor 1 and vascular endothelial growth factor and dramatically changed the micro-ribonucleic acid profile of fibroblast-secreted EMVs in vitro. The priming was followed by significant angiogenic and cardioprotective effects.CSp-EMVs alter fibroblast phenotype and secretome in a salutary positive-feedback loop. The phenotypic conversion of inert cells to therapeutically active cells reveals a novel mechanism for amplification of exosome bioactivity.
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Project description:To compare the clinical characteristics and outcomes of preeclamptic women presenting with a normal plasma angiogenic profile with those subjects who are characterized by an abnormal angiogenic profile.This was a secondary analysis of a prospective cohort study in women presenting to obstetrical triage at <37 weeks of gestation and diagnosed with preeclampsia within 2 weeks of enrollment and in whom angiogenic factors (sFlt1 and PlGF) measurements were available. Patients were divided into two groups based on their circulating levels of these factors described as a ratio; the sFlt1/PlGF ratio, non-angiogenic preeclampsia (sFlt1/PlGF ratio <85) and angiogenic preeclampsia (sFlt1/PlGF ratio ?85). The data are presented by sFlt1/PlGF category using median and quartile 1-quartile 3 for continuous variables and by frequency and sample sizes for categorical variables.In our cohort, the patients with non-angiogenic preeclampsia (N?=?46) were more obese [BMI: 35.2 (31.6, 38.7) versus 31.1 (28.0, 39.0), p?=?0.04], more likely to have preexisting diabetes (21.7% versus 2.0%, p?=?0.002) and presented at a later gestational age [35 (32, 37) versus 32 (29, 34) weeks, p?<?0.0001] as compared with women with angiogenic preeclampsia (N?=?51). Women with non-angiogenic preeclampsia had no serious adverse outcomes (elevated liver function tests/low platelets: 0% versus 23.5%, abruption: 0% versus 9.8%, pulmonary edema: 0% versus 3.9%, eclampsia: 0% versus 2.0 %, small for gestational age: 0% versus 17.7% and fetal/neonatal death: 0% versus 5.9%) as compared with women with angiogenic preeclampsia. The rate of preterm delivery <34 weeks was 8.7% in non-angiogenic preeclampsia compared with 64.7% in angiogenic preeclampsia (p?<?0.0001). Interestingly, delivery between 34 and 37 weeks and resource utilization (hospital admission days) were similar in the two groups.In contrast to the angiogenic form, the non-angiogenic form of preeclampsia is characterized by little to no risk of preeclampsia-related adverse outcomes, other than iatrogenic prematurity. Incorporation of angiogenic biomarkers in the evaluation of preeclampsia may allow accurate and early identification of severe disease.
| S-EPMC3744824 | biostudies-literature
Project description:Several studies have linked maternal asthma, excess BMI, and low vitamin D status with increased risk of Preeclampsia (PE) development. Given prior evidence in the literature and our observations from the subjects in the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we hypothesized that PE, maternal asthma, vitamin D insufficiency, and excess body mass index (BMI) might share both peripheral blood and placental gene signatures that link these conditions together. We used samples collected in the VDAART to investigate relationships between these four conditions and gene expression patterns in peripheral blood obtained at early pregnancy. We identified a core set of differentially expressed genes in all comparisons between women with and without these four conditions and confirmed them in two separate sets of samples. We confirmed the differential expression of the shared gene signatures in the placenta from an independent study of preeclampsia cases and controls and constructed the preeclampsia module using protein-protein interaction networks. CXC chemokine genes showed the highest degrees of connectivity and betweenness centrality in the peripheral blood and placental modules. The shared gene signatures demonstrate the biological pathways involved in preeclampsia at the pre-clinical stage and may be used for the prediction of preeclampsia.
| S-EPMC7550614 | biostudies-literature
Project description:Adipsin is a protease produced at high levels by adipose tissue. It is involved in complement activation and metabolic control. The objective of this study was to determine the changes in adipsin levels during different stages of normal pregnancy, and its association with obstetric outcomes, such as preeclampsia. This nested case-control study in a longitudinal cohort included normal pregnant (n?=?54) and preeclamptic (n?=?18) women, both followed throughout pregnancy. Additionally, some of the normal pregnant women were followed up three months postpartum (n?=?18). Healthy non-pregnant women were also studied during their menstrual cycle (n?=?20). The results of this study show that in healthy non-pregnant women, adipsin levels did not change significantly during the menstrual cycle. In normal pregnant women, adipsin levels were lower (p?<?0.01) when compared with non-pregnant healthy women, but these serum levels increased again during postpartum (p?<?0.001). Adipsin levels were significantly elevated in preeclamptic women in late pregnancy (P?<?0.01). A significant correlation was not found between leptin and adipsin during the three periods of gestation studied in healthy pregnant and preeclamptic women. Our results suggest that adipsin may be involved in pregnancy-associated metabolic changes. Moreover, the increase of adipsin levels towards late gestation in preeclamptic women could be related to the pathophysiology of this disease.
| S-EPMC4735521 | biostudies-literature
Project description:BackgroundExperimental studies suggest that shallow uterine cytotrophoblastic invasion in preeclampsia may be associated with alterations in estrogen metabolism. The objective of this study was to examine the association of parent estrogens and their metabolites between preeclamptics and normotensive controls at three time points during pregnancy. Methods Parent estrogens and their metabolites were measured in urine by high-performance liquid chromatography-tandem mass spectrometry in 66 singleton preeclampsia cases and 137 matched controls. Percent change in geometric means were estimated by general linear models adjusted for gestational age at sampling, maternal age, parity, race, body mass index, and use of assisted reproductive technologies. Results Urinary estradiol concentrations were approximately 50% higher in early pregnancy in preeclampsia cases than controls, but similar late in pregnancy. There was an approximate 20% reduction in total 2-pathway metabolites and 4-pathway metabolites in cases compared with controls in mid- and later pregnancy that was slightly attenuated with adjustment for BMI, and a reduction in 16-pathways in mid-pregnancy but not later. Conclusion(s) Our findings show that estradiol concentrations were elevated in preeclampsia versus controls in early pregnancy. In mid-pregnancy, all three estrogen metabolism (2-, 4-, and 16-) pathways showed some reduction in preeclampsia that appeared to continue for the 2- and 4-pathways in late pregnancy. We hypothesize that this may indicate that there is a generalized reduction in estrogen metabolism in preeclampsia rather than a deficit of specific enzymes, such as those involved in the 2-hydroxylation pathway.
| S-EPMC6681456 | biostudies-literature
Project description:Purpose: The goals of this study is to compare and profile the smallRNA transcriptome of the placenta in preeclamptic and normal patients using RNA sequencing. Methods: Placental and Placental vesicles (STB-EVs) smallRNA profiles of normal and preeclamptic patients were generated by deep sequencing using Illumina HISEQ. FASTq.gz files were compressed with OASIS compressor and alignment was done with OASIS 2.0 ( by trimmimng with trimmomatic, aligning using default OASIS 2.0 aligning papameters). Quantitative PCR validation was performed using TaqMan gene expression assays Results: This contains a set of three parallel smallRNA sequencing experiments involving placenta tissue, medium/large STB-EVs and small STB-EVs. Comparison between PE and normal pregnancy placental tissue revealed 134 (p-value of <0.05 ) while in medium/large STB-EVs, 101 and in small STB-EVs, 16 (adjusted P-value of <0.05) differentially expressed small RNA We identified a number of mechanistic and biomarker targets, which were validated with qRT–PCR and confirmed to be signifficantly DE. The differentially expressed analysis identified potential yet undescribed small RNAs that may contribute to the pathogenesis of preeclampsia or/and may act as biomarkers of the disease. Conclusions: Our study represents the first combined analysis of placenta, medium/large and small STB-EV transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results identified potential Placenta EV small RNA biomarkers that can help diagnose the preeclampsia
2021-12-17 | GSE190972 | GEO
Project description:Purpose: The goals of this study is to compare and profile the transcriptome of the placenta in preeclamptic and normal patients using RNA sequencing. Methods: Placental and Placental vesicles (STB-EVs) mRNA profiles of normal and preeclamptic patients were generated by deep sequencing using Illumina HISEQ. The sequence reads that passed quality filters were analyzed at the gene level HISAT2 followed by featureCounts. Quantitative PCR validation was performed using TaqMan gene expression assays Results: This contains a set of three parallel mRNA sequencing experiments involving placenta tissue, medium/large STB-EVs and small STB-EVs. Comparison between PE and normal pregnancy placental tissue revealed 18,070 genes from which 580 were upregulated and 563 were downregulated (p-value of <0.05 ) while in medium/large STB-EVs, revealed 14,216 genes from which 1,128 were upregulated and 833 were downregulated. In small STB-EVs, out of 23,322 genes, 232 were upregulated and 106 were downregulated) (adjusted P-value of <0.05) We identified a number of mechanistic and biomarker targets, which were validated with qRT–PCR and confirmed to be signifficantly DE. The differentially expressed analysis identified potential yet undescribed genes that may contribute to the pathogenesis of preeclampsia or/and may act as biomarkers of the disease. Conclusions: Our study represents the first detailed analysis of combined Placenta and placental extracellular vesicles (STB-EVs) transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results have identified potential STB-EV based small RNA biomarkers in preeclampsia.
2021-12-17 | GSE190971 | GEO
Project description:Glioblastoma multiforme (GBM) is a devastating tumour with abysmal prognoses. We desperately need novel approaches to understand GBM biology and therapeutic vulnerabilities. Extracellular vesicles (EVs) are membrane-enclosed nanospheres released locally and systemically by all cells, including tumours, with tremendous potential for intercellular communication. Tumour EVs manipulate their local environments as well as distal targets; EVs may be a mechanism for tumourigenesis in the recurrent GBM setting. We hypothesized that GBM EVs drive molecular changes in normal human astrocytes (NHAs), yielding phenotypically tumour-promoting, or even tumourigenic, entities. We incubated NHAs with GBM EVs and examined the astrocytes for changes in cell migration, cytokine release and tumour cell growth promotion via the conditioned media. We measured alterations in intracellular signalling and transformation capacity (astrocyte growth in soft agar). GBM EV-treated NHAs displayed increased migratory capacity, along with enhanced cytokine production which promoted tumour cell growth. GBM EV-treated NHAs developed tumour-like signalling patterns and exhibited colony formation in soft agar, reminiscent of tumour cells themselves. GBM EVs modify the local environment to benefit the tumour itself, co-opting neighbouring astrocytes to promote tumour growth, and perhaps even driving astrocytes to a tumourigenic phenotype. Such biological activities could have profound impacts in the recurrent GBM setting.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.
| S-EPMC5717433 | biostudies-literature