Late first trimester circulating microparticle proteins predict the risk of preeclampsia
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ABSTRACT:
SUBMITTER: McElrath TF
PROVIDER: S-EPMC7578826 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Late first trimester circulating microparticle proteins predict the risk of preeclampsia < 35 weeks and suggest phenotypic differences among affected cases.
McElrath Thomas F TF Cantonwine David E DE Gray Kathryn J KJ Mirzakhani Hooman H Doss Robert C RC Khaja Najmuddin N Khalid Malik M Page Gail G Brohman Brian B Zhang Zhen Z Sarracino David D Rosenblatt Kevin P KP
Scientific reports 20201021 1
We hypothesize that first trimester circulating micro particle (CMP) proteins will define preeclampsia risk while identifying clusters of disease subtypes among cases. We performed a nested case-control analysis among women with and without preeclampsia. Cases diagnosed < 34 weeks' gestation were matched to controls. Plasma CMPs were isolated via size exclusion chromatography and analyzed using global proteome profiling based on HRAM mass spectrometry. Logistic models then determined feature sel ...[more]
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Project description:BackgroundAbnormal maternal lipid concentrations are associated with increased risk of preeclampsia. However, previous studies mainly focused on fasting lipid concentrations, scarce data have been published on the relationship between postprandial triglyceride (TG) concentrations in the second trimester and the risk of preeclampsia. Our aim is to evaluate the potential of triglyceride (TG) concentrations at the time of oral lipid tolerance test (OLTT) measurement in the second trimester to predict preeclampsia and to elucidate the lipid metabolic changes related to these diseases.MethodsThis is a prospective cohort study of Pregnant women at 12-24 weeks of gestation undergone an OLTT in a university affiliated hospital between May 2019 and January 2020. Data were stratified into binaries according to the OLTT results. The receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off points of TG, HDL-C, LDL-C, sd-LDL, FFA, and BG for predicting preeclampsia.Results438 pregnant women were recruited to undergo an OLTT at 12-24 weeks of gestation. Among these, 24 women developed preeclampsia and 414 women remained normotensive. Women who subsequently developed preeclampsia had higher concentrations of 4-h postprandial TG than those who remained normotensive. In the linear logistic regression analyses of potential confounding factors, mid-trimester 4-h postprandial TG concentrations at the time of OLTT measurement were significantly higher in preeclamptic cases than in controls.ConclusionsDyslipidemia in the second trimester of pregnancy, particularly postprandial hypertriglyceridemia, appears to be associated with an increased risk of preeclampsia. Mid-trimester 4-h postprandial TG concentration at the time of OLTT measurement may be a potential predictive marker of preeclampsia. Trial registration Data of registration: 2018/10/15. Date of initial participant enrollment: 2019/05/01. Clinical trial identification number: chiCTR1800018884. URL of the registration site: http://www.chictr.org.cn/showproj.aspx?proj=25526 . Data sharing information: The data including individual participant data, detailed study protocols, statistical analysis plans will be shared upon request to the corresponding author.
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Project description: Not available
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Project description:The goal of this study was to further validate eight candidate genes identified in a microarray analysis of first trimester placentas in preeclampsia.Surplus chorionic villus sampling (CVS) specimens of 4 women subsequently diagnosed with preeclampsia (PE) and 8 control women (C) without preeclampsia analyzed previously by microarray and 24 independent additional control samples (AS) were submitted for confirmatory studies by quantitative real-time polymerase chain reaction (qRT-PCR).Downregulation was significant in FSTL3 in PE as compared to C and AS (p = .04). PAEP was downregulated, but the difference was only significant between C and AS (p = .002) rather than between PE and either of the control groups. Expression levels for CFH, EPAS1, IGFBP1, MMP12, and SEMA3C were not statistically different among groups, but trends were consistent with microarray results; there was no anti-correlation. S100A8 was not measurable in all samples, probably because different probes and primers were needed.This study corroborates reduced FSTL3 expression in the first trimester of preeclampsia. Nonsignificant trends in the other genes may require follow-up in studies powered for medium or medium/large effect sizes. qRT-PCR verification of the prior microarray of CVS may support the placental origins of preeclampsia hypothesis. Replication is needed for the candidate genes as potential biomarkers of susceptibility, early detection, and/or individualized care of maternal-infant preeclampsia.
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Project description:Introduction:The aim of the study was to evaluate and compare the spiral artery flow in mid first trimester (4-8 weeks) in cases of threatened abortion and in normal pregnancies. Material and methods:Spiral artery was sonographically evaluated in 50 patients comprising two groups of 25 women each. The first group included patients presenting with threatened miscarriage (vaginal bleeding/spotting with or without abdominal pain). The second group comprised of females who had no complications, but had no desire to continue the pregnancy. Spiral artery flow velocity measurements were performed using Color Doppler (Pulsatility Indices, Resistive Indices and Systolic/diastolic values) in mid first trimester (between 4-8 weeks of gestation), each measurement was performed twice. Statistical analysis was performed using Statistical package for social sciences software. Values were rounded off to two digits after decimal point. Results:Significant differences were noted in the spiral artery Doppler values in the two groups. In particular, the Resistive Indices was higher in cases of women with threatened miscarriage. The difference in Pulsatility Indices was also statistically significant between the two groups. Conclusion:Doppler values of spiral artery may be used as a useful parameter in assessing the prognosis in cases presenting with threatened miscarriage.
| S-EPMC6988462 | biostudies-literature
Project description:Preeclampsia is a severe placenta-related pregnancy disorder that is generally divided into two subtypes named early-onset preeclampsia (onset <34 weeks of gestation), and lateonset preeclampsia (onset ≥34 weeks of gestation), with distinct pathophysiological origins. Both forms of preeclampsia have been associated with maternal systemic inflammation. However, alterations in the placental immune system have been less well characterized. Here, we studied immunological alterations in early- and late-onset preeclampsia placentas using a targeted expression profile approach. RNA was extracted from snap-frozen placenta samples (healthy n=13, early-onset preeclampsia n=13, and late-onset preeclampsia n=6). The expression of 730 immune-related genes from the Pan Cancer Immune Profiling Panel was measured, and the data were analyzed Q10 in the advanced analysis module of nSolver software (NanoString Technology). The results showed that early-onset preeclampsia placentas displayed reduced expression of complement, and toll-like receptor (TLR) associated genes, specifically TLR1 and TLR4. Mast cells and M2 macrophages were also decreased in early-onset preeclampsia compared to healthy pl acentas. The findings were confirmed by an immunohistochemistry approach using 20 healthy, 19 early-onset preeclampsia, and 10 late-onset preeclampsia placentas. We conclude that the placental innate immune system is altered in early-onset preeclampsia compared to uncomplicated pregnancies. The absence of these alterations in late-onset preeclampsia placentas indicates dissimilar immunological profiles. The study revealed distinct pathophysiological processes in earlyonset and late-onset preeclampsia placentas and imply that a tailored treatment to each subtype is desirable.
2021-12-13 | GSE190639 | GEO
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Project description:Whether HPV is causative of pregnancy complications is uncertain. E6 and E7 affect functions underling preeclampsia (PET) in cultured trophoblasts, but whether E6 and E7 is produced in the placenta is uncertain. Here, we investigated whether E6/E7 was expressed in the placentae from pregnancies with PET, other pregnancy complications (fetal growth restriction (FGR) and diabetes mellitus), and uncomplicated pregnancies. Placental tissues collected from two geographical locations were subjected to RNAscope analyses of high- and low- risk E6/E7, and individual HPV types identified using an HPV array. High-risk E6/E7 expression was increased in both PET cohorts, (81% and 86% of patients positive for high-risk HPV DNA compared to 13% of control patients). Various HPV types were identified. Although HPV 18 was the most frequent in all cohorts, the majority of individuals had multiple HPV types (55% of the PET compared to 25% of the control cohort). Further evidence that E6 and E7 is present early when placental pathology underlying preeclampsia is established, is provided with the finding of high-risk E6/E7 in the first-trimester placenta anchoring trophoblast. In conclusion, E6/E7 expression and multiple HPV types were frequent in placentae from preeclampsia-complicated pregnancies.
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