Early pathways, biomarkers, and four distinct molecular subclasses of preeclampsia: The intersection of clinical, pathological, and high-dimensional biology studies

Than, Nándor Gábor; Posta, Máté; Györffy, Dániel; Orosz, László; Oròsz, G.; Rossi, Simona W.; Ambrus-Aikelin, Géza; Szilágyi, András; Nagy, S.; Hupuczi, Petronella; Török, Olga; Tarca, Adi L.; Erez, Offer; Papp, Zoltán; Romero, Roberto

doi:10.1016/j.placenta.2022.03.009

Cited by 31 publications

(21 citation statements)

References 105 publications

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“…Herein, we did not perform a meta-analysis since different patient groups, and different basic methods limit the comparability of numerous studies. However, we investigated transcriptomic changes in pre-eclampsia in a recent publication [ 72 ].…”

Section: Resultsmentioning

confidence: 99%

Proteoglycans: Systems-Level Insight into Their Expression in Healthy and Diseased Placentas

Oravecz

Balogh

Romero

et al. 2022

IJMS

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Proteoglycan macromolecules play key roles in several physiological processes (e.g., adhesion, proliferation, migration, invasion, angiogenesis, and apoptosis), all of which are important for placentation and healthy pregnancy. However, their precise role in human reproduction has not been clarified. To fill this gap, herein, we provide an overview of proteoglycans’ expression and role in the placenta, in trophoblast development, and in pregnancy complications (pre-eclampsia, fetal growth restriction), highlighting one of the most important members of this family, syndecan-1 (SDC1). Microarray data analysis showed that of 34 placentally expressed proteoglycans, SDC1 production is markedly the highest in the placenta and that SDC1 is the most upregulated gene during trophoblast differentiation into the syncytiotrophoblast. Furthermore, placental transcriptomic data identified dysregulated proteoglycan genes in pre-eclampsia and in fetal growth restriction, including SDC1, which is supported by the lower concentration of syndecan-1 in maternal blood in these syndromes. Overall, our clinical and in vitro studies, data analyses, and literature search pointed out that proteoglycans, as important components of the placenta, may regulate various stages of placental development and participate in the maintenance of a healthy pregnancy. Moreover, syndecan-1 may serve as a useful marker of syncytialization and a prognostic marker of adverse pregnancy outcomes. Further studies are warranted to explore the role of proteoglycans in healthy and complicated pregnancies, which may help in diagnostic or therapeutic developments.

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Section: Resultsmentioning

confidence: 99%

Proteoglycans: Systems-Level Insight into Their Expression in Healthy and Diseased Placentas

Oravecz

Balogh

Romero

et al. 2022

IJMS

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“…PLGF showed excellent AUCs, while sFlt-1 and sFlt-1/PLGF showed perfect AUCs. Best cut off values and performance characteristics are shown in table (5). In order to predict PE susceptibility, a logistic regression analysis was done utilizing the angiogenic biomarkersratio as variables.…”

Section: Resultsmentioning

confidence: 99%

“…PE susceptibility is also greatly influenced by genetic components of angiogenesis and immunological interactions between the mother and fetus. Early-onset or preterm PE, in contrast to late-onset PE, can be predicted more accurately in the first trimester by a combination of maternal characteristics, biophysical indications, and biochemical markers (5) . According to several studies, Angiogenic variables may be useful in distinguishing between diseases such gestational thrombocytopenia and PE and superimposed PE, immune thrombocytopenic purpura, renal illness, chronic hypertension, and pregnant hypertension (6) .…”

Section: Discussionmentioning

confidence: 99%

Angiogenic Biomarkers (sFlt / PLGF): An Approach for Clinical Integration of Pre-eclampsia

Elmazny

Abo-Hashem²,

El-Hussiny³

et al. 2022

The Egyptian Journal of Hospital Medicine

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Background: One of the most important pregnancy problems is pre-eclampsia (PE). PE is caused by changes in the circulating levels of angiogenic agents. Endothelial dysfunction is caused by elevated levels of antiangiogenic factors like soluble fms-like tyrosine kinase-1(sFlt-1) and decreased levels of angiogenic factors like placental growth factor (PlGF). Objective: This study's objective is to assess the significance of alternation of angiogenic balance as a preeclamptic marker and their association to PE severity. Patients and Methods: One hundred pregnant women in third trimester participated in this case-control study, with 40 having mild PE, 40 having severe PE, and 20 healthy pregnant ladies as control. It was done in Clinical Pathology and Obstetrics and Gynecology Departments of Mansoura University Hospitals during a period from "November 2020 to April 2022". Clinical and laboratory tests on all individuals were performed, including CBC, LDH, sFlt-1 in the serum, PLGF, liver function tests, renal function tests. Results: In comparison to the control group, greater levels of sFlt-1 and sFlt-1/PLGF and lower levels of PLGF were present in all cases of mild and severe PE (p0.001 for each). Additionally, severe cases demonstrated significant high levels of sFlt-1 and sFlt-1/PLGF and significant low levels of PLGF with superior AUCs when compared to moderate instances (AUC=0.999). Conclusion: sFlt-1, PLGF and sFlt-1/PLGF ratio may have a role in the prediction of severity of PE, and thus diagnosis of PE, thus may be used in management of PE.

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“…For example, the quantification of blood hCG, PP13/galectin-13, and PSG1 has emerged as crucial in the detection of pregnancy or being pregnancy complications, together with preeclampsia, from maternal blood [71,72]. Since the discovery of cell-free fetal DNA (cffDNA) in the maternal circulation by Lo et al in 1997 [73], the fast-evolving non-invasive prenatal diagnostics (NIPT) technologies have revolutionized prenatal screening of genetic defects primarily based on the detection of cffDNA in a small amount of maternal blood [74]. Shortly after, Lo et al additionally identified circulating placental/fetal RNA (cpRNA) in the maternal circulation [75] and determined the earliest gestational age (4th week) at which these cpRNAs are present in the maternal circulation.…”

Section: Liquid Biopsy Of the Placentamentioning

confidence: 99%

“…Decreased uteroplacental perfusion and ischemic stress cause an imbalance in angiogenic and antiangiogenic factors, ensuing in endothelial damage, systemic infection, and multiorgan failure [3,[7][8][9][10][11][12][13][14][15][16][17][18][19][20]. In term period preeclampsia, the impact of diverse chronic stressors consisting of obesity, diabetes, and kidney, metabolic or autoimmune disease is more dominant [21][22][23][24][25][26][27][28][29][30] and maternal vascular and endothelial reaction can also be more sensitive to placental factors [31,32]. Genetic elements related to angiogenesis and immune interactions among the mother and the fetus also are key for the susceptibility to preeclampsia [33][34][35][36][37][38][39][40][41].…”

Section: Introduction 1 Preeclampsia Syndromementioning

confidence: 99%

Biomarkers in Prediction of Preeclampsia

Naser

Shehata

2022

IJPSAT

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Preeclampsia is being pregnant-specific, and notably contributes to maternal, and perinatal morbidity and mortality worldwide. An effective predictive test for preeclampsia could facilitate early diagnosis, focused surveillance and well timed delivery; however, restrained alternatives presently exist. A first-trimester screening algorithms has been evolved and demonstrated to expect preterm preeclampsia, with poor utility for term disease, wherein the greatest burden lies. Biomarkers consisting of sFlt-1 and placental growth factor also are now getting used clinically in cases of suspected preterm preeclampsia; their high negative predictive value allows assured exclusion of disease in women with normal results, however sensitivity is modest. There has been a concerted attempt to become aware of ability novel biomarkers that could enhance prediction. These in large part originate from organs concerned in preeclampsia’s pathogenesis, which includes placental, cardiovascular and urinary biomarkers. This review outlines the clinical imperative for an effective test and those already in use and summarises modern-day preeclampsia biomarker studies.

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Early pathways, biomarkers, and four distinct molecular subclasses of preeclampsia: The intersection of clinical, pathological, and high-dimensional biology studies

Cited by 31 publications

References 105 publications

Proteoglycans: Systems-Level Insight into Their Expression in Healthy and Diseased Placentas

Proteoglycans: Systems-Level Insight into Their Expression in Healthy and Diseased Placentas

Angiogenic Biomarkers (sFlt / PLGF): An Approach for Clinical Integration of Pre-eclampsia

Biomarkers in Prediction of Preeclampsia

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