Biomarker For Preeclampsia Research Articles

Integrated bioinformatics analysis reveals that CCBP2 and GPR87 are new GPCR-associated biomarkers for preeclampsia

BackgroundPreeclampsia (PE) is a multifaceted pregnancy syndrome marked by multiple system involvement and a significant contributor to maternal mortality. This condition is characterized by a critical lack of early diagnostic measures and viable therapeutic options, underscoring an urgent need for the identification of reliable markers with both diagnostic and therapeutic potential.MethodsThis study utilized Weighted Gene Co-expression Network Analysis (WGCNA) to explore the role of G protein-coupled receptors (GPCRs) in the pathogenesis of PE.ResultsOur analysis pinpointed CCBP2 (ACKR2) and GPR87 as central PE-associated GPCRs. Experimental validation of these findings revealed that both CCBP2 and GPR87 significantly inhibit the proliferation, migration, and invasion of trophoblast cells—core phenomena underlying the pathology of PE.ConclusionThus, our findings add valuable candidates to the growing list of biomarkers for preeclampsia and offer promising targets for future therapeutic development.

Untargeted Urinary Volatilomics Reveals Hexadecanal as a Potential Biomarker for Preeclampsia.

Preeclampsia (PE) is a severe hypertensive pregnancy disorder characterized by endothelial dysfunction, placental ischemia and oxidative stress; however, reliable non-invasive biomarkers for early detection are limited. In this study, untargeted solid-phase microextraction with gas chromatography-mass spectrometry (SPME-GC-MS) was used to analyze volatile organic compounds in the urine of 45 women with PE and 46 healthy controls. Among the 29 metabolites identified, hexadecanal-a product of lipid peroxidation and sphingolipid metabolism-was found to be the most significant, with an area under the receiver operating characteristic (ROC) curve of 0.618, highlighting its diagnostic potential. This result emphasizes the role of hexadecanal in oxidative stress and placental dysfunction, which are central to the pathophysiology of PE. The results support hexadecanal as a potential non-invasive biomarker while demonstrating the efficacy of SPME-GC-MS in identifying metabolic disorders associated with PE, paving the way for further research to confirm its clinical utility for early diagnosis and risk assessment.

Exploring the ceRNA network involving AGAP2-AS1 as a novel biomarker for preeclampsia

Preeclampsia (PE) is an important research subject in obstetrics. Nevertheless, the underlying mechanisms of PE remain elusive. PE-related expression datasets (GSE96983, GSE96984 and GSE24129) were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, the differentially expressed messenger RNAs (DE-mRNAs), DE-microRNA (DE-miRNAs) and DE-long non-coding RNA (DE-lncRNAs) between PE and control cohorts were identified, and the ceRNA network was constructed. Then candidate hub genes were obtained through five algorithms by the protein-protein intersection (PPI) network of the mRNAs. Further, five hub genes were identified by receiver operating characteristic (ROC) curve and gene expression profiles: DAXX, EFNB1, NCOR2, RBBP4 and SOCS1. The function of 5 hub genes was analyzed and the interaction between drugs and hub genes was predicted. A total of 5 small molecule drugs were predicted, namely benzbromarone, 9,10-phenanthrenequinone, chembl312032, insulin and aldesleukin. AGAP2-AS1 was mainly located in exosome and cytoplasm. Agap2-as1-related regulatory subnetworks were extracted from ceRNA networks which included 41 mRNAs, 2 miRNAs and 1 lncRNA, including the regulated relationship pairs AGAP2-AS1-hsa-miR-497-5p-SRPRB, and AGAP2-AS1-hsa-miR-195-5p-RPL36. In summary, we constructed a competitive endogenous RNA (ceRNA) network to identify five potential biomarkers (DAXX, EFNB1, NCOR2, SOCS1 and RBBP4) of PE. The in-depth analysis of the AGAP2-AS1 regulatory network will help to uncover more important molecules closely related to PE and provide a scientific Reference.

Epigenetic biomarker for preeclampsia-associated preterm birth and potential preventative medicine.

Preterm birth (PTB) has dramatically increased within the population (i.e. >10%) and preeclampsia is a significant sub-category of PTB. Currently, there are no practical clinical parameters or biomarkers which predict preeclampsia induced PTB. The current study investigates the potential use of epigenetic (DNA methylation) alterations as a maternal preeclampsia biomarker. Non-preeclampsia term births were compared to preeclampsia PTBs to identify DNA methylation differences (i.e. potential epigenetic biomarker). Maternal buccal cell cheek swabs were used as a marker cell for systemic epigenetic alterations in the individuals, which are primarily due to environmentally induced early life or previous generations impacts, and minimally impacted or associated with the disease etiology or gestation variables. A total of 389 differential DNA methylation regions (DMRs) were identified and associated with the presence of preeclampsia. The DMRs were genome-wide and were predominantly low CpG density (<2 CpG/100 bp). In comparison with a previous PTB buccal cell epigenetic biomarker there was a 15% (60 DMR) overlap, indicating that the majority of the DMRs are unique for preeclampsia. Few previously identified preeclampsia genes have been identified, however, the DMRs had gene associations in the P13 K-Akt signaling pathway and metabolic gene family, such as phospholipid signaling pathway. Preliminary validation of the DMR use as a potential maternal biomarker used a cross-validation analysis on the samples and provided 78% accuracy. Although prospective expanded clinical trials in first trimester pregnancies and clinical comparisons are required, the current study provides the potential proof of concept a preeclampsia epigenetic biomarker may exist. The availability of a preeclampsia PTB maternal susceptibility biomarker may facilitate clinical management and allow preventative medicine approaches to identify and treat the preeclampsia condition prior to its occurrence.

Development and validation of preeclampsia predictive models using key genes from bioinformatics and machine learning approaches.

Preeclampsia (PE) poses significant diagnostic and therapeutic challenges. This study aims to identify novel genes for potential diagnostic and therapeutic targets, illuminating the immune mechanisms involved. Three GEO datasets were analyzed, merging two for training set, and using the third for external validation. Intersection analysis of differentially expressed genes (DEGs) and WGCNA highlighted candidate genes. These were further refined through LASSO, SVM-RFE, and RF algorithms to identify diagnostic hub genes. Diagnostic efficacy was assessed using ROC curves. A predictive nomogram and fully Connected Neural Network (FCNN) were developed for PE prediction. ssGSEA and correlation analysis were employed to investigate the immune landscape. Further validation was provided by qRT-PCR on human placental samples. Five biomarkers were identified with validation AUCs: CGB5 (0.663, 95% CI: 0.577-0.750), LEP (0.850, 95% CI: 0.792-0.908), LRRC1 (0.797, 95% CI: 0.728-0.867), PAPPA2 (0.839, 95% CI: 0.775-0.902), and SLC20A1 (0.811, 95% CI: 0.742-0.880), all of which are involved in key biological processes. The nomogram showed strong predictive power (C-index 0.873), while FCNN achieved an optimal AUC of 0.911 (95% CI: 0.732-1.000) in five-fold cross-validation. Immune infiltration analysis revealed the importance of T cell subsets, neutrophils, and NK cells in PE, linking these genes to immune mechanisms underlying PE pathogenesis. CGB5, LEP, LRRC1, PAPPA2, and SLC20A1 are validated as key diagnostic biomarkers for PE. Nomogram and FCNN could credibly predict PE. Their association with immune infiltration underscores the crucial role of immune responses in PE pathogenesis.

Linking EDC-laden food consumption and modern lifestyle habits with preeclampsia: A non-animal approach to identifying early diagnostic biomarkers through biochemical alterations

Preeclampsia (PE), a pregnancy complication characterized by new-onset hypertension with or without proteinuria and/or end-organ damage, and it may be influenced by exposure to endocrine-disrupting chemicals present in processed foods and modern lifestyles. This study explores the potential link using a non-animal approach to identify early diagnostic biomarkers for preeclampsia. Seventy pregnant women aged 21–41 years participated, and completed questionnaires assessing socio-demographic factors, Suboptimal Health Status Questionnaire scores for fatigue, digestive, cardiovascular, immune, and mental health issues, and exposure to endocrine-disrupting chemicals from processed food consumption and daily product use. Peripheral blood samples were analyzed for hormone profiles, complete blood count, and liver function tests (LFT). Statistical analysis revealed that mothers above 27 years old, with a Body Mass Index exceeding 32.59 Kg/m2, and a Mean Arterial Pressure of 108.5 mmHg exhibited a potential obesogenic effect on preeclampsia development. Socio-demographic factors like, lower economic class, housewife status, primiparous pregnancy, non-graduate education, and rural residence were significantly associated with results. Analysis of biochemical parameters revealed that serum creatinine, blood urea, total protein, platelet count, blood urea nitrogen, bilirubin profile, LFT profile, and thyroid profile showed potential detrimental effects on kidney, liver, muscle, and thyroid function in preeclampsia patients. Notably, PC, serum urea, bilirubin, total protein, serum glutamic-oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), and thyroid stimulating hormone (TSH) levels were significantly associated with preeclampsia in individuals reporting higher exposure to endocrine disrupting chemicals (EDCs). Minor biochemical alterations were also observed with dairy product consumption. SHS-25 analysis indicated a significant increase in fatigue, and digestive, cardiovascular, immune, and mental health-related issues in patients. Probably, biochemical alterations due to EDC exposure from processed foods and modern lifestyle habits contribute to organ dysfunction in preeclampsia. Identifying these potential biomarkers may pave the way for the development of non-invasive, early diagnostic tools for improved preeclampsia management. This research emphasizes the importance of non-animal testing methods for assessing EDC-related health risks in pregnancy and contributes to the advancement of early PE diagnosis strategies.

Pre-eclampsia intronic polyadenylation enriched in VEGFA-VEGFR2 signaling pathway

AimsThis study aims to reveal transcriptome-wide intronic polyadenylation (IPA) events associated with Pre-eclampsia (PE). BackgroundPre-eclampsia (PE) is a potentially life-threatening complication of pregnancy, affecting both maternal and fetal health. However, our understanding of the underlying molecular mechanisms of PE remains limited. ObjectiveIn this study, we conducted a transcriptome-wide analysis of gene expression levels and intronic polyadenylation (IPA) events in samples of patients with PE. We also conducted motif analysis and scanned the microRNA targeting IPA network. MethodWe collected 90 PE-related samples from GEO database. IPA events were analyzed using IPAfinder software from hg38 alignment files from STAR. Miranda software was used to perform miRNA target gene prediction. Differentially expressed genes (DEG) were evaluated using edgeR with log2 fold change >1 and adjusted p-value <0.05. Function enrichment was performed through Clusterprofiler. ResultOur analysis revealed that genes in the VEGFA-VEGFR2 signaling pathway were functionally enriched with IPA events related to PE. We observed a negative correlation between gene expression levels and IPA events in VEGFA-VEGFR2 pathway. We identified LIN28B and AGO2 as the most significantly binding motifs to IPA sites. Furthermore, our analysis of miRNA binding sites associated with these IPA events revealed the central regulatory roles of miR-193b and miR-365a in IPA genes. ConclusionOur findings suggest that transcriptome data-mining might be a useful approach in future studies aimed at identifying potential biomarkers for PE.

Development of non-invasive biomarkers for pre-eclampsia through data-driven cardiovascular network models

Computational models can be at the basis of new powerful technologies for studying and classifying disorders like pre-eclampsia, where it is difficult to distinguish pre-eclamptic patients from non-pre-eclamptic based on pressure when patients have a track record of hypertension. Computational models now enable a detailed analysis of how pregnancy affects the cardiovascular system. Therefore, new non-invasive biomarkers were developed that can aid the classification of pre-eclampsia through the integration of six different measured non-invasive cardiovascular signals. Datasets of 21 pregnant women (no early onset pre-eclampsia, n = 12; early onset pre-eclampsia, n = 9) were used to create personalised cardiovascular models through computational modelling resulting in predictions of blood pressure and flow waveforms in all major and minor vessels of the utero-ovarian system. The analysis performed revealed that the new predictors PPI (pressure pulsatility index) and RI (resistance index) calculated in arcuate and radial/spiral arteries are able to differentiate between the 2 groups of women (t-test scores of p < .001) better than PI (pulsatility index) and RI (Doppler calculated in the uterine artery) for both supervised and unsupervised classification. In conclusion, two novel high-performing biomarkers for the classification of pre-eclampsia have been identified based on blood velocity and pressure predictions in the smaller placental vasculatures where non-invasive measurements are not feasible.

Complete blood count as a biomarker for preeclampsia with severe features diagnosis: a machine learning approach

ObjectiveThis study introduces the complete blood count (CBC), a standard prenatal screening test, as a biomarker for diagnosing preeclampsia with severe features (sPE), employing machine learning models.MethodsWe used a boosting machine learning model fed with synthetic data generated through a new methodology called DAS (Data Augmentation and Smoothing). Using data from a Brazilian study including 132 pregnant women, we generated 3,552 synthetic samples for model training. To improve interpretability, we also provided a ridge regression model.ResultsOur boosting model obtained an AUROC of 0.90±0.10, sensitivity of 0.95, and specificity of 0.79 to differentiate sPE and non-PE pregnant women, using CBC parameters of neutrophils count, mean corpuscular hemoglobin (MCH), and the aggregate index of systemic inflammation (AISI). In addition, we provided a ridge regression equation using the same three CBC parameters, which is fully interpretable and achieved an AUROC of 0.79±0.10 to differentiate the both groups. Moreover, we also showed that a monocyte count lower than 490/mm3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$490 /mm^{3}$$\\end{document} yielded a sensitivity of 0.71 and specificity of 0.72.ConclusionOur study showed that ML-powered CBC could be used as a biomarker for sPE diagnosis support. In addition, we showed that a low monocyte count alone could be an indicator of sPE.SignificanceAlthough preeclampsia has been extensively studied, no laboratory biomarker with favorable cost-effectiveness has been proposed. Using artificial intelligence, we proposed to use the CBC, a low-cost, fast, and well-spread blood test, as a biomarker for sPE.

SARS-CoV-2 seroprevalence and preeclampsia markers in Mozambican pregnant women with perinatal loss

BackgroundSARS-CoV-2 infection during pregnancy is known to be associated with poor pregnancy outcomes, including pre-eclampsia (PE), prematurity, perinatal and maternal mortality. Data on the burden of SARS-CoV-2 infection among pregnant women and their offspring in Sub-Saharan Africa is limited. We aimed to estimate SARS-CoV-2 seroprevalence and determine PE biomarkers in Mozambican pregnant women with perinatal loss.MethodsA cross-sectional study was conducted among women who had a fetal or an early neonatal death at the Maputo Central Hospital (MCH), Mozambique. Anti-SARS-CoV-2 IgG/IgM were determined in maternal and umbilical cord blood and PE biomarkers (sFlt-1 and PIGF) in maternal blood. SARS-CoV-2 RT-PCR was performed in placenta and fetal lung biopsies from participants found to be SARS-CoV-2 seropositive.ResultsA total of 100 COVID-19 unvaccinated women were included in the study from March 2021 to April 2022. Total SARS-CoV-2 antibodies were detected in 68 [68%; 95CI (58 – 76)] maternal and 55 [55%; 95CI (54 – 74)] cord blood samples. SARS-CoV-2 IgM was detected in 18 cord blood samples and a positive placental RT-PCR in three of these participants. The proportion of women with moderate to high sFlt-1/PIGF ratio was higher in SARS-CoV-2 seropositive women than in those seronegative (71.2% vs 28.8%, p = 0.339), although the difference was not statistically significant.ConclusionsSARS-CoV-2 seroprevalence among Mozambican women with perinatal loss was high during the second pandemic year, and there was evidence of vertical transmission in stillbirths. Findings also suggest that maternal SARS-CoV-2 infection may increase the risk of developing PE.

Proteomic Analysis Reveals Differential Protein Expression in Placental Tissues of Early-Onset Preeclampsia Patients.

Preeclampsia, a significant cause of maternal and perinatal morbidity and mortality, remains poorly understood, in terms of its pathogenesis. This study aims to uncover novel and effective biomarkers for preeclampsia by conducting a comparative analysis of differential proteins in placentas from early onset preeclampsia (EOPE) and normal pregnancies. Utilizing tandem mass tag (TMT)-based quantitative proteomics, we identified differentially expressed proteins in placental tissues from 15 EOPE patients and 15 normal pregnant women. These proteins were subsequently validated by using parallel reaction monitoring (PRM). Our analysis revealed a total of 59 differentially expressed proteins, with 25 up-regulated and 34 down-regulated proteins in EOPE placental tissues compared to those from normal pregnancies. Validation through PRM confirmed the differential expression of 6 proteins. Our findings suggest these 6 proteins could play crucial roles in the pathogenesis of EOPE, highlighting the potential involvement of the estrogen signaling pathway and dilated cardiomyopathy (DCM) pathway in the development of preeclampsia. The data were deposited with the ProteomeXchange Consortium via the iProX partner repository with the identifier PXD055025.

Fibronectin as a predictor of preeclampsia

Since preeclampsia first emerged a few centuries ago, a substantial portion of humanity has been tormented by this disease, which has jeopardized and disrupted mankind. Numerous biological markers, including ENDOGLIN, PIGF (placental growth factor), SFLT 1(soluble fms like-tyrosine kinase 1), and PAPP-A (pregnancy associated plasma protein-A), suggest preeclampsia. It was beneficial for detecting preeclampsia, even if there was frequent mortality and morbidity among mothers because of the anticipated latency. Then another marker, fibronectin, was added to the picture. A better preeclampsia prognosis leads substantially to an overall decrease in maternal morbidity and mortality. The primary organ that manufactures circulating fibronectin, occasionally referred to as serum fibronectin, is the liver. To enable the extracellular and intracellular matrix to communicate and regulate cell behavior, fibronectin, an extracellular matrix element, primarily interacts with integrin receptors. Fibronectin is a diagnostic marker for a variety of ailments, such as muscular dystrophy, ovarian and stomach cancers, and gestational diabetes. Inflammatory changes result in the release of fibronectin into the bloodstream, and the main triggering factor of preeclampsia is the infiltration of various trophoblasts that injures endothelial tissues and induces inflammation. Therefore, the primary goal of our study was to establish that fibronectin is a biomarker of preeclampsia. To elucidate our perspective and evaluate whether fibronectin is relevant in preeclampsia prediction, we will conduct a qualitative evaluation of prior research and juxtapose it with the findings of the present study. Thus, early detection of preeclampsia could decrease the rate of maternal mortality and morbidity.

Routine ante-natal screening using maternal risk factors and biomarkers for preeclampsia in 11-13+6 weeks of gestation.

Prediction of preeclampsia in first trimester can lead to early initiation of preventative measures, as well as timely therapeutic intervention, that will prevent the maternal and perinatal morbidity and mortality. This study, prediction of preeclampsia at 11-13+6 weeks of gestation, was conducted by using serum placental growth factor (PlGF), serum pregnancy associated plasma protein - A (PAPP-A), uterine artery Doppler indices, and mean arterial pressure (MAP), in low-risk pregnant women. It is an observational longitudinal prospective study. Pregnant women with singleton pregnancies of gestational age 11-13+6 weeks were recruited. MAP, bilateral uterine artery Doppler indices, serum PAPP-A, and PlGF were measured. The follow-up of the patients was regularly done till termination of pregnancy and incidence of preeclampsia were noted. Qualitative variables were compared using Chi-square/Fisher exact test, and sensitivity and specificity of each test were analyzed. Among 139 women, 27 (19%) developed preeclampsia, out of which 10 had early preeclampsia and 17 developed late preeclampsia. By combining all the parameters, the sensitivity in detecting early preeclampsia was found to be 70% and for late preeclampsia cases, 64.7%. The sensitivity of all the parameters in predicting cases of preeclampsia in general is 66.7%, specificity is 74.1%, PPV is 38.3%, and NPV is 72%. The maternal biomarkers serum PAPP-A, serum PlGF, uterine artery PI, MAP have sensitivity of 70% in detecting early preeclampsia cases and for late preeclampsia cases, 64.71%, in first trimester and it will help in early initiation of preventative measures as well as timely therapeutic intervention.

Exosomal miRNAs as Potential Biomarkers for Preeclampsia: miR-1283 Has the Highest Expression, while miR-152-3p Has the Lowest Expression

BACKGROUND: Preeclampsia management is necessary, as it is one of the leading causes of death during pregnancy. Exosomal microRNAs (miRNAs) can serve as biomarkers for early detection, diagnosis, and prognosis of preeclampsia. NanoStrings is an effective method for identifying exosomal miRNA due to their high sensitivity and ability to work with small amounts of miRNA; however, the analysis using this method for determining preeclampsia biomarker is still limited. Therefore, this study was conducted to utilize the NanoStrings method in identifying preeclampsia biomarkers related to its underlying pathophysiology.METHODS: This study involved 12 pregnant women at 20–40 weeks of gestation, including 6 preeclampsia women and 6 normotension women. The miRNAs from plasma exosomes were processed using NanoStrings method with NanoString nCounter SPRINT Profiler. Enrichment analysis of The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways were performed to examine the pathophysiological pathways of preeclampsia, using the DIANA–miRPath v3.0.RESULTS: Forty-eight miRNAs were downregulated and 7 were upregulated (miR-1283, miR-613, miR-520a-3p, miR-3185, miR-556-3p, miR-1973, and miR-598-3p) in women with preeclampsia. The highest expression was observed in miR-1283 (log fold-change: 3.69) and the most lowest expression was in miR-152-3p (log fold-change: 1.41). Enrichment analysis showed that the most upregulated miRNAs pathways was estrogen signaling pathway, and the most downregulated was Hippo signaling pathways.CONCLUSION: miR-1283 has the highest expression, while and miR-152-3p has the lowest expression in preeclampsia women. These miRNAs are shown to be linked to specific pathways, shedding light on the pathophysiology of preeclampsia, and may serve as promising biomarkers.KEYWORDS: exosomes, biomarker, miRNAs, pathophysiology, preeclampsia, pregnancy

Hsa_circ_0088196 Predicts Adverse Pregnancy Outcomes in Preeclampsia Patients and Contributes to Endothelial Cell Injury Via Modulating the miR-145-5p/FLT1 Axis.

Preeclampsia (PE) is a specific hypertension-related disease in pregnancies, causing adverse pregnancy outcomes. Endothelial cell dysfunction is a major etiology of PE, of which the regulation could affect disease progression. This study focused on hsa_circ_0088196, evaluating its clinical significance in PE and its effect on endothelial cell injury, aiming to identify a novel biomarker for PE and complete its regulating mechanism in disease development. The study enrolled 165 normal pregnancies and 165 pregnancies with gestational hypertension. The significance of hsa_circ_0088196 in discriminating gestational hypertension, predicting PE, and predicting adverse pregnancy outcomes was evaluated based on its serum expression. The effect and mechanism of hsa_circ_0088196 in HUVEC injury were assessed by CCK8, Transwell, ELISA, and western blotting. Significant downregulation of hsa_circ_0088196 could distinguish gestational hypertension pregnancies and predict the risk of PE. Gestational hypertension pregnancies developed PE showed a lower serum hsa_circ_0088196 level, which also discriminated PE patients, predicted severe conditions and adverse pregnancy outcomes. Overexpressing hsa_circ_0088196 alleviated the enhanced proliferation, migration, inflammation, and angiogenesis by hypoxia/reoxygenation (H/R), which was reversed by miR-145-5p. Silencing miR-145-5p showed similar effects on H/R-induced endothelial cell injury, which was reversed by FLT1. Moreover, FLT1 was positively regulated by hsa_circ_0088196, indicating its involvement in the regulation of HUVEC injury by hsa_circ_0088196. Reduced serum hsa_circ_0088196 served as a biomarker for the diagnosis of gestational hypertension, risk evaluation of PE, and the prediction of adverse pregnancy outcomes. hsa_circ_0088196 suppressed endothelial cell injury induced by H/R through modulating the miR-145-5p/FLT1 axis.

Circulating vascular endothelial growth factor receptor-3, a pro-lymphangiogenic and pro-angiogenic mediator, is decreased in pre-eclampsia.

To compare circulating levels of vascular endothelial growth factor receptor 3 (VEGFR-3) in women with pregnancy-induced hypertension (PIH) and in non-pregnant (NP) and healthy pregnant (HP) women. We conducted a case-control study including PIH (n = 135), HP (n = 68), and NP (n = 49) women from southeastern Brazil. PIH were diagnosed according to international guidelines, and defined as gestational hypertension (GH, n = 61) or pre-eclampsia (n = 74). VEGFR-3 was measured in plasma using ELISA. Plasma VEGFR-3 was increased in HP (1207 pg/mL) compared with NP (133 pg/mL) women; however, PIH (729 pg/mL) patients exhibited lower levels than HP women (both p < 0.05). In addition, plasma VEGFR-3 was decreased in pre-eclampsia compared with GH (537 versus 980 pg/mL; p < 0.05). When pre-eclampsia was classified according to different clinical presentations, plasma VEGFR-3 was further decreased in the cases identified as pre-eclampsia with severe features, preterm pre-eclampsia, and pre-eclampsia accompanied by small for gestational age (all p < 0.05). Our data indicate reduced circulating VEGFR-3 levels in patients with PIH, specifically in those diagnosed with pre-eclampsia. Moreover, decreased VEGFR-3 was associated with adverse clinical outcomes in pre-eclampsia. These findings expand previous evidence of reduced VEGFR-3 expression in pre-eclampsia. Future studies should investigate whether it can be used as a predictive biomarker and/or therapeutic target for pre-eclampsia.

Abstract Tu003: The angiotensinogen/vasorin ratio in peripheral blood, a biomarker for preeclampsia

Background: Preeclampsia (PE) significantly impacts maternal and perinatal health worldwide. Despite limited treatment options, predictive tests could help in early diagnosis and personalized treatment/prevention strategies. Current biomarker, such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta growth factor (PIGF) offer reasonable negative predictive values, but their use as positive predictive markers is limited. Using unbiased discovery proteomics on urine extracellular vesicles (EV), followed by verification by ELISA and western blotting we identified a novel biomarker candidate for PE, vasorin (VASN), which is significantly decreased in PE, along with a known mediator of PE, angiotensinogen (AGT), that was significantly increased in PE as biomarker candidates. Hypothesis: Levels of AGT, VASN and their ratios in peripheral blood can be utilized as biomarkers for PE. Goals/Aims: 1) To determine gestational age (GA)-dependence of AGT, VASN and AGT/VASN plasma levels in human and murine pregnancy. 2) To assess disease association of AGT, VASN and AGT/VASN in a cohort of pregnant women with PE with severe features (sPE) and gestational age-matched normotensive pregnant women (NTP) and in a murine model of PE. Methods: Plasma was collected from GA-matched NTP and sPE. Timed pregnant mice were injected with adenoviral vector (AD) encoding sFLT-1 on embryonic day 10.5 (mouse PE), or with AD encoding enhanced green fluorescent protein injection (mouse control). AGT and VASN were measured by ELISA in human samples and were quantified by western blotting in murine samples. Results: AGT and AGT/VASN showed negative correlations with GA, while VASN levels showed positive correlation with GA in NTP and in mouse controls. PlGF and sFLT-1 levels had weak/no correlations with GA. AGT and AGT/VASN were significantly higher in sPE and mouse PE, while VASN was significantly decreased in sPE and mouse PE as compared to NTP and mouse controls, respectively. To differentiate between sPE vs NTP with receiver operating characteristic curve (ROC) for AGT/VASN: AUC (0.90), Sensitivity =92%, Specificity = 85% at AGT/VASN&gt;81.6. Conclusion: AGT and AGT/VASN ratio increase, and VASN decrease can serve as biomarkers for PE.

Evaluation of diagnostic potential of maternal serum ischemia modified albumin in cases of pre-eclampsia.

The underlying causes and mechanisms of pre-eclampsia (PE), its exact etiology remains unclear and poorly understood. Hypoxia, ischemia, and oxidative stress induced by free radicals have been associated with development of PE. Ischemia-modified albumin (IMA) is a chemically modified albumin due to oxidative stress. IMA, a serum biomarker of hypoxia, ischemia, and oxidative free radicals is a potential biomarker for PE. The aim of the current proposal was to study serum IMA as a diagnostic biomarker of pre-eclampsia (PE) in pregnant females and to evaluate the correlation between serum IMA and different markers of pre-eclampsia (BP, urinary protein, LFT, KFT, serum total protein & uric acid). A total of 60 pregnant women aged between 21 and 35 years were recruited (30 PE cases and 30 normal pregnancy). Serum IMA was measured by spectrophotometric method developed by Bar-Or D. BP and biochemical parameters (urinary protein, LFT, KFT, serum total protein & uric acid) were also assayed and compared between two groups. Correlation analysis was done for analyzing the relationship between serum IMA and biochemical parameters. The mean serum IMA was significantly higher in normotensive pregnant females (0.93 ABSU) than PE cases (0.71 ABSU). Kidney function and liver function parameters were more deranged in PE cases than in controls. Serum IMA was positively correlated with serum creatinine (r=0.322), serum uric acid (r=0.54) and urinary protein (0.376) whereas negatively correlated with total serum bilirubin (r=-0.515) and serum albumin (r=-0.380). Elevated serum IMA concentrations in normotensive pregnant controls as compared to PE cases suggest that apart from ongoing ischemia and oxidative stress in placenta IMA values are influenced by many other mechanisms in pregnancy.

Maternal Serum Cyclophilin A: A Predictive Biomarker of Preeclampsia in South Indian Women

Maternal Serum Cyclophilin A: A Predictive Biomarker of Preeclampsia in South Indian Women

Biochemical and Oxidative Biomarkers in Preeclampsia.

To determine the biochemical and oxidative stress parameters as biomarkers in preeclampsia. Cross-sectional analytical study. Place and Duration of the Study: Departments of Obstetrics / Gynaecology and Biochemistry, Quaid-e-Azam Medical College, Bahawalpur, Pakistan, from September 2022 to February 2023. Women with preeclampsia were selected based on blood pressure exceeding 140/90 mmHg and proteinuria levels exceeding 300 mg/24 hours or showing a +1 on a dipstick test. Normotensive pregnant women were selected as controls. Venous blood was taken and centrifuged, and routine biochemical methods were used to estimate serum lipid profile levels and minerals. The estimation of oxidative stress enzymes was carried out manually using special chemicals. Student's t-test and Pearson's correlation were applied to analyse the result. The study included 228 subjects: 114 preeclampsia patients and 114 normal pregnant women as controls. The mean systolic blood pressure was measured at 166.25 mmHg and the diastolic blood pressure was 92.80 mmHg (p <0.001). All lipid profile estimations showed notable abnormalities, but the mean level of triglycerides (TGs) (214.90 ± 15.59 mg/dl) in preeclamptic patients was significantly elevated (p <0.05). In terms of minerals, all were deranged but magnesium (1.37 ± 0.35 mg/dl) and calcium (7.55 ± 0.45 mg/dl) were significantly decreased (p <0.05). All oxidative enzyme levels were increased (p <0.05) but malondialdehyde (MDA) with a mean level of 2.58 ± 0.40 nmol/ml was significantly elevated. The Pearson's correlation of these parameters with blood pressure also showed a positive association. Total cholesteroltriglyceride in the lipid profile, calcium and magnesium in minerals, and MDA in oxidative parameters were markedly deranged and exhibited significant associations with the severity of the disease, so could be used as disease biomarkers of preeclampsia. Preeclampsia, Gestational hypertension, Proteinuria, Lipid profile, Minerals, Oxidative stress.