Activation of the Receptor for Advanced Glycation End Products System in Women with Severe Preeclampsia

Oliver, Emily A.; Buhimschi, Catalin S.; Dulay, Antonette T.; Baumbusch, Margaret A.; Abdel-Razeq, Sonya S.; Lee, Sarah Y.; Zhao, Guomao; Jing, Shichu; Pettker, Christian M.; Buhimschi, Irina A.

doi:10.1210/jc.2010-1418

Cited by 35 publications

(35 citation statements)

References 33 publications

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“…Here, we also found that the levels of sRAGE in umbilical cord blood were significantly decreased in women with sPE, and we did not detect any correlations between these levels and those of inflammatory cytokines. Another study reported that cord blood sRAGE levels were not affected by sPE, but the affected women had higher serum and amniotic fluid sRAGE and esRAGE levels than those expected for gestational age [34] . Therefore, the low level of sRAGE in umbilical cord blood might be associated with the activation of the AGE-RAGE system in the neonate and the oxidative stress or inflammatory responses in the maternal-fetal interface, or might be influenced by the higher levels in amniotic fluid, and unaffected by inflammation or PE.…”

Section: Discussionmentioning

confidence: 95%

“…Increased levels of RAGE in women with PE have been shown in some [21] , but not all studies [22] . Compared with nonpregnant women, the sRAGE serum level was found reduced in pregnancy, but its course produced conflicting results.…”

Section: Discussionmentioning

confidence: 99%

“…Little is known regarding the levels of circulating AGEs in pregnancy. One small study reported elevated serum AGEs in women with PE [6] , whereas another small study suggested that gestational diabetes was associated with elevated concentrations of AGEs in serum [7] .…”

Section: Discussionmentioning

confidence: 99%

“…Little is known about circulating AGEs in pregnancy. One small study reported elevated serum AGEs in women with PE [6] , whereas another small study suggested that gestational diabetes was associated with elevated serum concentrations of AGEs [7] . AGEs trigger proinflammatory, profibrotic, and procoagulatory cellular responses that are capable of damaging tissues, often targeting particular organs.…”

mentioning

confidence: 99%

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Accumulation of Advanced Glycation End Products Involved in Inflammation and Contributing to Severe Preeclampsia, in Maternal Blood, Umbilical Blood and Placental Tissues

Chen

Zhang

Yue

et al. 2016

Gynecol Obstet Invest

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Objective: To investigate the expression of advanced glycation end products (AGEs) and the receptor for AGE (RAGEs) in maternal blood, umbilical blood and placental tissues in women with severe preeclampsia (sPE) as well as any association with inflammatory processes. Methods: The expressions of AGEs, RAGE, tumor necrosis factor-alpha (TNF)-α and vascular cell adhesion molecule-1 (VCAM)-1 in placental tissues were measured using immunohistochemistry. The levels of AGEs, RAGE, TNF-α and VCAM-1 in maternal blood, umbilical blood and placental extracts were assessed using enzyme-linked immunosorbent assays. Placental RAGE, TNF-α and VCAM-1 mRNA expression levels were determined by PCR. Placental AGEs, RAGE, TNF-α and VCAM-1 protein levels were determined by western blotting. Results: The levels of AGEs, TNF-α and VCAM-1 in the maternal tissues and umbilical blood were significantly higher in the sPE group than in the normal pregnancy (NP) controls (p < 0.05). The serum level of sRAGE in the umbilical blood was lower in the sPE group than in the NP controls (p < 0.05), while sRAGE was higher in the maternal blood of sPE than in the NP (p < 0.05). The maternal serum levels of AGEs were positively correlated with that of TNF-α and VCAM-1 in the maternal blood. There were no correlations between the levels of RAGE, TNF-α or VCAM-1 in maternal blood or umbilical serum. There were no correlations between the levels of sRAGE and TNF-α or VCAM-1 in maternal blood or umbilical serum. The levels of AGEs were positively correlated with those of TNF-α and VCAM-1 in placental lysates. Conclusion: AGEs and RAGE appear to act as important mediators in regulating the inflammatory pathways of preeclampsia.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Accumulation of Advanced Glycation End Products Involved in Inflammation and Contributing to Severe Preeclampsia, in Maternal Blood, Umbilical Blood and Placental Tissues

Chen

Zhang

Yue

et al. 2016

Gynecol Obstet Invest

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“…However, AGEs are dramatically increased in some disorders; especially in those patients who suffer from oxidative stress with conditions such as diabetes, rheumatoid arthritis, systemic lupus erythematosus, Alzheimer's disease, or in cigarette smokers. Olier et al [9] have found that the expression of AGEs in maternal serum of patients with pre-eclampsia was significantly higher when compared to the expression in normal pregnant women and non-pregnant women. Gueds et al [10] have also shown that the accumulation of AGEs can cause oxidative stress in the placenta and placental vascular dysfunction, and thus lead to pre-eclampsia.…”

Section: Biological Activity Of Agesmentioning

confidence: 99%

Study of the relationship between AGEs and oxidative stress damage to trophoblast cell mitochondria

Jiang

Yan

2017

Ginekol Pol

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Objectives: To study the influence of AGEs on placental trophoblast mitochondria oxidative stress, and to explore the possible pathogenesis which may participate in pre-eclampsia. Material and methods:Human trophoblast cells from early pregnancy were cultured by an enzyme-digestion method. When trophoblast cells reached approximately 70-80% after passages, they were incubated with pre-eclampsia serum for 24 hours. A fluorescent dye assay was applied to measure the mitochondrial membrane potential; ELISA was used to measure the activity of the mitochondrial permeability transition pore. mtDNA was detected by Real-time fluorescence quantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR). We continued to culture one group of cells with pre-eclampsia maternal serum, and other cells were pulsed with 600 mg/L AGEs. Cells were incubated for 16 hours before assaying the levels of mitochondrial oxidative stress damage. Results:The levels of mitochondria oxidative stress damage in the AGEs group were higher than in the pre-eclampsia group 1 and pre-eclampsia group 2. There was no statistically significant difference in mitochondrial oxidative stress damage between the pre-eclampsia group 1 and group 2. Conclusions:The AGEs are involved in the pathogenesis of pre-eclampsia, possibly through the enhancement of mitochondrial oxidative stress damage.

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Automated REcognition of Tissue‐associated Erythrocytes (ARETE)—a new tool in tissue cytometry

Heindl

Seewald²,

Thalhammer

et al. 2013

Cytometry Pt A

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Automated microscopic image analysis of immunofluorescence-stained targets on tissue sections is challenged by autofluorescent elements such as erythrocytes, which might interfere with target segmentation and quantification. Therefore, we developed an automated system (Automated REcognition of Tissue-associated Erythrocytes; ARETE) for in silico exclusion of erythrocytes. To detect erythrocytes in transmission images, a cascade of boosted decision trees of Haar-like features was trained on 8,640/ 4,000 areas (15 3 15 pixels) with/without erythrocytes from images of placental sections (4 mm). Ground truth data were generated on 28 transmission images. At least two human experts labelled the area covered by erythrocytes. For validation, output masks of human experts and ARETE were compared pixel-wise against a mask obtained from majority voting of human experts. F1 score, specificity, and Cohen's j coefficients were calculated. To study the influence of erythrocyte-derived autofluorescence, we investigated the expression levels of a protein (receptor for advanced glycated end products; RAGE) in placenta and number of Ki-67-positive/cytokeratin 8-positive epithelial cells in colon sections. ARETE exhibited high sensitivity (99.87%) and specificity (99.81%) on a training-subset and processed transmission images (1,392 3 1,024 pixels) within 4 sec. ARETE and human expert's F1-scores were 0.55 versus 0.76, specificities 0.85 versus 0.92 and Cohen's j coefficients 0.41 versus 0.68. A ranking of Cohen's j coefficient by the scale of Fleiss certified ''good agreement'' between ARETE and the human experts. Applying ARETE, we demonstrated 4-14% false-positive RAGE-expression in placenta, and 18% falsely detected proliferative epithelial cells in colon, caused by erythrocyte-autofluorescence. ARETE is a fast system for in silico reduction of erythrocytes, which improves automated image analysis in research and diagnostic pathology. '

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Activation of the Receptor for Advanced Glycation End Products System in Women with Severe Preeclampsia

Abstract: Fetal membranes are a rich source of sRAGE. Elevated maternal serum and amniotic fluid sRAGE and esRAGE, paralleled by increased RAGE expression in the amniochorion, suggest activation of this system in sPE.

Cited by 35 publications

References 33 publications

Accumulation of Advanced Glycation End Products Involved in Inflammation and Contributing to Severe Preeclampsia, in Maternal Blood, Umbilical Blood and Placental Tissues

Accumulation of Advanced Glycation End Products Involved in Inflammation and Contributing to Severe Preeclampsia, in Maternal Blood, Umbilical Blood and Placental Tissues

Study of the relationship between AGEs and oxidative stress damage to trophoblast cell mitochondria

Automated REcognition of Tissue‐associated Erythrocytes (ARETE)—a new tool in tissue cytometry

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