Dynamic proteome in enigmatic preeclampsia: An account of molecular mechanisms and biomarker discovery

Mary, Sheon; Patil, Gouri V.; Kulkarni, Asmita; Kulkarni, Mahesh J.; Joshi, Sadhana; Mehendale, Savita; Giri, Ashok P.

doi:10.1002/prca.201100089

Cited by 11 publications

(13 citation statements)

References 141 publications

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“…We hypothesized that similar temporal placenta-related protein expression patterns 224 should be conserved in mouse pregnancies, therefore, we explored our EN- PE is based on the presence of maternal hypertension and proteinuria [38]. Previous 252 transcriptomic [39][40][41][42][43][44][45] and proteomic [2,[46][47][48][49][50] Our findings of serum protein levels during a normal pregnancy are consistent with those 261 from previous studies. They are in line with the ranges reported in healthy pregnancies and have 262 similar patterns during the pregnancy as previous results [51][52][53][54][55][56][57][58][59].…”

Section: Comparative Analysis Of Serological Ga Estimation Between Thsupporting

confidence: 72%

Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia

Hao

You

Chen

et al. 2018

Preprint

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1Background: Placental protein expression plays a crucial biological role during normal and 2 complicated pregnancies. We hypothesized that: (1) circulating pregnancy-associated, placenta-3 related protein levels throughout gestation reflect the uncomplicated, full-term temporal 4 progression of human gestation, and effectively estimates gestational ages (GAs); (2) 5 pregnancies with underlying placental pathology, such as preeclampsia (PE), are associated with 6 disruptions in this GA estimation in early gestation; (3) malfunctions of this GA estimation can 7 be employed to identify impending PE. In addition, to explore the underlying biology and PE 8 etiology, we set to compare protein gestational patterns of human and mouse, using pregnant 9 heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like 10 symptoms. 11Methods: Serum levels of circulating placenta-related proteins -leptin (LEP), chorionic 12 somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like 13 tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)-were quantified by ELISA in 14 blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 15 20 PE subjects with 61 samples). Linear multivariate analysis of the targeted serological protein 16 levels was performed to estimate the normal GA. Logarithmic transformed mean-squared errors 17 of GA estimations were used to identify impending PE. Then the human gestational protein 18 patterns were compared to those in the pregnant HO-1 mice. 19Results: An elastic net (EN)-based gestational dating model was developed (R 2 = 0.76) and 20 validated (R 2 = 0.61) using the serum levels of the 6 proteins at various GAs from women with 21 normal uncomplicated pregnancies (n = 10 for training and n = 6 for validation). In pregnancies 22 complicated by PE (n = 14), the EN model was not (R 2 = -0.17) associated with GA at sampling 23 3 3 in PE. Statistically significant deviations from the normal GA EN model estimations were 24 observed in PE-associated pregnancies between GAs of 16-30 weeks (P = 0.01). The EN model 25 developed with 5 proteins (ELA excluded due to the lack of robustness of the mouse ELA essay) 26 performed similarly on normal human (R 2 = 0.68) and WT mouse (R 2 = 0.85) pregnancies. 27 Disruptions of this model were observed in both human PE-associated (human: R 2 = 0.27) and 28 mouse HO-1 Het (mouse: R 2 = 0.30) pregnancies. LEP out performed sFlt-1 and PlGF in 29 differentiating impending PE at early human and late mouse gestations. 30 Conclusions: As revealed in both human and mouse GA EN analyses, temporal serological 31 placenta-related protein patterns are tightly regulated throughout normal human pregnancies and 32 can be significantly disrupted in pathologic PE states. LEP changes earlier during gestation than 33 the well-established late GA PE biomarkers (sFlt-1 and PlGF). Our HO-1 Het mouse analysis 34 provides direct evidence of the causative action of HO-1 deficiency in LEP upregulation in a...

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Section: Comparative Analysis Of Serological Ga Estimation Between Thsupporting

confidence: 72%

Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia

Hao

You

Chen

et al. 2018

Preprint

View full text Add to dashboard Cite

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“…There are about 50 candidate genes that are involved in developing PE, of which eight genes are encoded for RNA. 2 At present, there is no good marker for early prediction, so diagnosis and intervention can be given usually after the occurrence of clinical symptoms. For example, STOX1 gene, which is associated with the expression of the maternal allele has a role in trophoblast dysfunction in PE.…”

Section: Introductionmentioning

confidence: 99%

Application of iTRAQ proteomics in identification of the differentially expressed proteins of placenta of pregnancy with preeclampsia

Feng

Wang

et al. 2018

J of Cellular Biochemistry

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Objective To explore the differential protein profile of preeclampsia and identify its potential biomarker. Methods Around 20 pregnant women with preeclampsia (preeclampsia group) and 20 normal‐term pregnancy (normal group) were collected from 2017 to 2018 in the study. Total protein of placenta tissues was extracted, denaturized, deoxidized, and enzymolyzed. The sample was labeled with isobaric tags for relative and absolute quantitation (iTRAQ) and analyzed with mass spectrum to identify differentially expressed proteins. Results There were 37 proteins, which were differentially expressed with significance (P < 0.05). Among them, 17 proteins were upregulated and 20 proteins were downregulated with significance in the placenta of preeclampsia group compared with control group, those proteins may have an induction or protection function during the development of preeclampsia. Conclusion iTRAQ technology can effectively screen the differentially expressed proteins in the placenta, which can effectively diagnose the preeclampsia during pregnancy.

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“…It has been conjectured that the primary underlying cause of the PE is the abnormal placentation because of inadequate trophoblast invasion. Factors that contribute majorly to such a pathophysiology are hypoxia, apoptosis, oxidative stress, inflammation and imbalance in angiogenic factors (Mary et al, 2012). Hypoxic placenta as a result of reduced blood flow, suffers from oxidative stress, leading to increased shedding of trophoblast debris by apoptotic process.…”

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confidence: 99%

“…This is followed by trophoblast invasion into maternal deciduas to remodel spiral arteries from lowcapacity high-resistance to high-capacity low-resistance vessels (Chaiworapongsa, Chaemsaithong, Yeo, & Romero, 2014). Factors that contribute majorly to such a pathophysiology are hypoxia, apoptosis, oxidative stress, inflammation and imbalance in angiogenic factors (Mary et al, 2012). This leads to reduced remodeling of spiral arteries, eventually causing decreased blood flow to the placenta (Lambert, Brichant, Hartstein, Bonhomme, & Dewandre, 2014).…”

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confidence: 99%

“…Ultimately, it causes pathophysiological problems such as placental ischemia, immunological and generalized endothelial dysfunctions (Roberts, 2014). Factors that contribute majorly to such a pathophysiology are hypoxia, apoptosis, oxidative stress, inflammation and imbalance in angiogenic factors (Mary et al, 2012). It is still unclear whether these are etiological factors or secondary effects.…”

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confidence: 99%

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Differential accumulation of vimentin fragments in preeclamptic placenta

et al. 2017

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Preeclampsia is a pregnancy complication that is the result of abnormal placentation because of inadequate trophoblast invasion into spiral arteries that prevent normal blood flow to the placenta. We report the alteration in vimentin protein proteolysis in placenta of normotensive and preeclamptic women, which is known to have a role in many physiological functions other than its major function in the structural integrity of the cell. Placental proteome from normotensive (n = 25) and preeclamptic pregnancies (n = 25) showed eight differentially accumulated protein spots of vimentin (proteolytic fragments) by two-dimensional electrophoresis. Immunoblots of normotensive and preeclamptic placenta revealed a difference in proteolytic processing of vimentin. In particular, lower molecular weight vimentin fragments of 32 and 20 kDa were 3.3 and 2.6-fold (p < 0.0001) higher, respectively, in preeclampsia compared with normotensive placenta.

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Dynamic proteome in enigmatic preeclampsia: An account of molecular mechanisms and biomarker discovery

Cited by 11 publications

References 141 publications

Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia

Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia

Application of iTRAQ proteomics in identification of the differentially expressed proteins of placenta of pregnancy with preeclampsia

Differential accumulation of vimentin fragments in preeclamptic placenta

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