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Journal ArticleDOI

Differences in the proteome profile in placenta from normal term and preeclamptic preterm pregnancies.

01 May 2007-Proteomics Clinical Applications (Wiley-VCH Verlag)-Vol. 1, Iss: 5, pp 446-456
TL;DR: Endothelial monocyte‐activating polypeptide was shown to be down‐regulated in preeclampsia by 2‐DE and MS, and three proteins identified by MS to be Hsp27, catalase, and glucose‐regulated protein were confirmed by Western blot analysis to be significantly up‐regulated to be involved in regulatory pathways activated by stress.
Abstract: The aim of this study was to use proteomic approaches to examine differences in protein expression in placentae from normal term and preterm preeclamptic pregnancies and to validate the data thus obtained by other independent methods. Using 2-DE we found that 80% of the proteins were present in both normal and preeclamptic placentae. However, 26 proteins in the normal term placentae were not matched in the preterm preeclamptic group. Six proteins showed increased intensity and one protein was down-regulated in preeclampsia. Four of the seven proteins that were altered in preeclampsia were further analyzed by Western blot and immunohistochemistry. Identification by MS techniques revealed these proteins to be involved in regulatory pathways activated by stress. This is significant because preeclampsia is a multisystem disorder in human pregnancies that results in considerable oxidative and nitrative stress. Three proteins identified by MS to be Hsp27, catalase, and glucose-regulated protein were confirmed by Western blot analysis to be significantly up-regulated in preeclampsia. Endothelial monocyte-activating polypeptide was shown to be down-regulated in preeclampsia by 2-DE and MS.
Citations
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Journal ArticleDOI
TL;DR: The vascular stress test of pregnancy identifies women with a previously unrecognized at risk vascular system and promotes the development of preeclampsia, a pregnancy‐specific syndrome characterized by hypertension, proteinuria and edema that resolves on delivery of the placenta.

262 citations

Journal ArticleDOI
TL;DR: This review will describe the advantages and limitations of relevant animals such as the guinea pig, sheep, and nonhuman primate models that have been used to study the role of the placenta in fetal growth disorders, preeclampsia, or other maternal diseases during pregnancy.
Abstract: Abnormalities of placental development and function are known to underlie many pathologies of pregnancy, including spontaneous preterm birth, fetal growth restriction, and preeclampsia. A growing body of evidence also underscores the importance of placental dysfunction in the lifelong health of both mother and offspring. However, our knowledge regarding placental structure and function throughout pregnancy remains limited. Understanding the temporal growth and functionality of the human placenta throughout the entirety of gestation is important if we are to gain a better understanding of placental dysfunction. The utilization of new technologies and imaging techniques that could enable safe monitoring of placental growth and function in vivo has become a major focus area for the National Institutes of Child Health and Human Development, as evident by the establishment of the "Human Placenta Project." Many of the objectives of the Human Placenta Project will necessitate preclinical studies and testing in appropriately designed animal models that can be readily translated to the clinical setting. This review will describe the advantages and limitations of relevant animals such as the guinea pig, sheep, and nonhuman primate models that have been used to study the role of the placenta in fetal growth disorders, preeclampsia, or other maternal diseases during pregnancy.

143 citations

Journal ArticleDOI
01 Dec 2008-Placenta
TL;DR: The targets and extent of nitration of enzymes, receptors, transporters and structural proteins may markedly influence placental cellular function in both physiologic and pathologic settings.

114 citations


Cites background from "Differences in the proteome profile..."

  • ...We have further demonstrated the up-regulation of Gp96 in a proteomic screen in the preeclamptic placenta [157]....

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Journal ArticleDOI
04 Jun 2019-PLOS ONE
TL;DR: A catalogue of proteome changes in maternal plasma proteome that precede the diagnosis of preeclampsia and can distinguish among early and late phenotypes is presented.
Abstract: Objectives To identify maternal plasma protein markers for early preeclampsia (delivery <34 weeks of gestation) and to determine whether the prediction performance is affected by disease severity and presence of placental lesions consistent with maternal vascular malperfusion (MVM) among cases. Study design This longitudinal case-control study included 90 patients with a normal pregnancy and 33 patients with early preeclampsia. Two to six maternal plasma samples were collected throughout gestation from each woman. The abundance of 1,125 proteins was measured using high-affinity aptamer-based proteomic assays, and data were modeled using linear mixed-effects models. After data transformation into multiples of the mean values for gestational age, parsimonious linear discriminant analysis risk models were fit for each gestational-age interval (8–16, 16.1–22, 22.1–28, 28.1–32 weeks). Proteomic profiles of early preeclampsia cases were also compared to those of a combined set of controls and late preeclampsia cases (n = 76) reported previously. Prediction performance was estimated via bootstrap. Results We found that 1) multi-protein models at 16.1–22 weeks of gestation predicted early preeclampsia with a sensitivity of 71% at a false-positive rate (FPR) of 10%. High abundance of matrix metalloproteinase-7 and glycoprotein IIbIIIa complex were the most reliable predictors at this gestational age; 2) at 22.1–28 weeks of gestation, lower abundance of placental growth factor (PlGF) and vascular endothelial growth factor A, isoform 121 (VEGF-121), as well as elevated sialic acid binding immunoglobulin-like lectin 6 (siglec-6) and activin-A, were the best predictors of the subsequent development of early preeclampsia (81% sensitivity, FPR = 10%); 3) at 28.1–32 weeks of gestation, the sensitivity of multi-protein models was 85% (FPR = 10%) with the best predictors being activated leukocyte cell adhesion molecule, siglec-6, and VEGF-121; 4) the increase in siglec-6, activin-A, and VEGF-121 at 22.1–28 weeks of gestation differentiated women who subsequently developed early preeclampsia from those who had a normal pregnancy or developed late preeclampsia (sensitivity 77%, FPR = 10%); 5) the sensitivity of risk models was higher for early preeclampsia with placental MVM lesions than for the entire early preeclampsia group (90% versus 71% at 16.1–22 weeks; 87% versus 81% at 22.1–28 weeks; and 90% versus 85% at 28.1–32 weeks, all FPR = 10%); and 6) the sensitivity of prediction models was higher for severe early preeclampsia than for the entire early preeclampsia group (84% versus 71% at 16.1–22 weeks). Conclusion We have presented herein a catalogue of proteome changes in maternal plasma proteome that precede the diagnosis of preeclampsia and can distinguish among early and late phenotypes. The sensitivity of maternal plasma protein models for early preeclampsia is higher in women with underlying vascular placental disease and in those with a severe phenotype.

80 citations

Journal ArticleDOI
22 Jan 2020-Placenta
TL;DR: Omics integration approach offers the promise to understand molecular mechanisms in preeclampsia despite the lack of coherent biomarkers in all omics studies, inhibin is a potential preeclamptic biomarker supported by GWAS, transcriptomics and DNA methylation evidence.

48 citations

References
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Journal ArticleDOI
TL;DR: It is proposed that poorly perfused placental tissue releases a factor(s) into the systemic circulation that injuries endothelial cells and set in motion a dysfunctional cascade of coagulation, vasoconstriction, and intravascular fluid redistribution that results in the clinical syndrome of preeclampsia.

1,827 citations

Journal ArticleDOI
TL;DR: There are genetic components to susceptibility, but the relative contributions of maternal and fetal genotypes are still unclear and whole-genome mapping could ultimately define the causative genes.

1,244 citations

Journal ArticleDOI
TL;DR: The present review summarizes the current knowledge about the cellular functions, expression, and clinical implications of the 90-kDa molecular chaperone family and some approaches for future research.

976 citations

01 Jan 1998
TL;DR: The 90-kDa molecular chaperone family (which comprises, among other proteins, the 90- kDa heat-shock protein, hsp90 and the 94-kda glucose-regulated protein, grp94) has become an increasingly active subject of research in the past couple of years as discussed by the authors.
Abstract: The 90-kDa molecular chaperone family (which comprises, among other proteins, the 90- kDa heat-shock protein, hsp90 and the 94-kDa glucose-regulated protein, grp94, major molecular chaperones of the cytosol and of the endoplasmic reticulum, respectively) has become an increasingly active subject of research in the past couple of years. These ubiquitous, well-conserved proteins account for 1-2% of all cellular proteins in most cells. However, their precise function is still far from being elucidated. Their involvement in the aetiology of several autoimmune diseases, in various infections, in recognition of malignant cells, and in antigen-presentation already demonstrates the essential role they likely will play in clinical practice of the next decade. The present review summarizes our current knowledge about the cellular functions, expression, and clinical implications of the 90-kDa molecular chaperone family and some approaches for future research. pharmacol. ther. 79(2):129-168, 1998. © 1998 Elsevier Science Inc.

943 citations

Journal ArticleDOI
TL;DR: In late gestation increased oxidative stress is seen in pregnancies complicated by diabetes, IUGR, and preeclampsia in association with increased trophoblast apoptosis and deportation and altered placental vascular reactivity.
Abstract: Pregnancy is a state of oxidative stress arising from increased placental mitochondrial activity and production of reactive oxygen species (ROS), mainly superoxide anion. The placenta also produces other ROS including nitric oxide, carbon monoxide, and peroxynitrite which have pronounced effects on placental function including trophoblast proliferation and differentiation and vascular reactivity. Excessive production of ROS may occur at certain windows in placental development and in pathologic pregnancies, such as those complicated by preeclampsia and/or IUGR, overpowering antioxidant defenses with deleterious outcome. In the first trimester, establishment of blood flow into the intervillous space is associated with a burst of oxidative stress. The inability to mount an effective antioxidant defense against this results in early pregnancy loss. In late gestation increased oxidative stress is seen in pregnancies complicated by diabetes, IUGR, and preeclampsia in association with increased trophoblast apoptosis and deportation and altered placental vascular reactivity. Evidence for this oxidative stress includes increased lipid peroxides and isoprostanes and decreased expression and activity of antioxidants. The interaction of nitric oxide and superoxide produces peroxynitrite, a powerful prooxidant with diverse deleterious effects including nitration of tyrosine residues on proteins thus altering function. Nitrative stress, subsequent to oxidative stress is seen in the placenta in preeclampsia and diabetes in association with altered placental function.

738 citations