Endogenous soluble receptor for advanced glycation endproducts is increased in preeclampsia

Faßhauer, Mathias; Seeger, Jeannette; Waldeyer, Theresa; Schrey, S; Ebert, Thomas; Lössner, Ulrike; Blüher, Matthias; Stümvoll, Michael; Faber, R.; Stepan, Holger

doi:10.1097/hjh.0b013e3283060c5c

Cited by 10 publications

(8 citation statements)

References 18 publications

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“…Our findings of lower sRAGE in pregnant women with T1DM who subsequently developed PE (compared with those who remained normotensive) are novel and clearly different from those found in previous cross-sectional studies of pregnant women without diabetes. [23][24][25][26]28 The latter showed elevated sRAGE and/or AGE associated with the presence of PE. They do not provide data on the levels of sRAGE in early pregnancy, nor do they address levels in the presence of T1DM.…”

Section: Discussionmentioning

confidence: 94%

“…21,22 Several cross-sectional studies in pregnant women without diabetes have shown elevated RAGE and AGEs to be associated with vascular dysfunction in PE versus controls. [23][24][25][26][27][28] However, these studies have not addressed whether an altered sRAGE-AGE system precedes or is a consequence of PE. Furthermore, no data have been reported on the causal associations of sRAGE and AGEs with PE in T1DM, a condition associated with a four-fold increase in PE.…”

Section: Introductionmentioning

confidence: 99%

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Reduced soluble receptor for advanced glycation end‐products (sRAGE) scavenger capacity precedes pre‐eclampsia in Type 1 diabetes

Hanssen

et al. 2012

BJOG

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Objective Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE. Design Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset. Setting Antenatal clinics. Population Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21). Methods Maternal serum levels of sRAGE (total circulating pool), Nε-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays. Main outcome measures Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE–). Results In DM PE+ versus DM PE–, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P < 0.05). Further, reflecting the net sRAGE scavenger capacity, sRAGE : hydroimidazolone was significantly lower in the second trimester (P < 0.05) and sRAGE : AGE and sRAGE : CML tended to be lower in the first trimester (P < 0.1) in women with T1DM who subsequently developed PE versus those who did not. These conclusions persisted after adjusting for prandial status, glycated haemoglobin (HbA1c), duration of diabetes, parity and mean arterial pressure as covariates. Conclusions In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Reduced soluble receptor for advanced glycation end‐products (sRAGE) scavenger capacity precedes pre‐eclampsia in Type 1 diabetes

Hanssen

et al. 2012

BJOG

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“…The evidence concerning maternal adiponectin concentrations in the presence of preeclampsia is inconsistent: higher [41, 58, 59, 70, 92, 112, 113, 116, 130, 159], lower [31, 33, 34, 63, 125], and similar adiponectin concentrations [119, 120, 145, 160] have been reported in patients with preeclampsia compared to normal pregnant women. This alleged inconsistency may be due to differences in the study population characteristics, definitions of preeclampsia (mild vs. severe, early vs. late onset), sample size or methods by which adiponectin concentrations were determined.…”

Section: Discussionmentioning

confidence: 99%

Maternal serum adiponectin multimers in preeclampsia

Mazaki‐Tovi¹,

Romero²,

Vaisbuch³

et al. 2009

Jpme

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Objective Obesity, insulin resistance, and dyslipidemia are associated with preeclampsia. Recently, “adipose tissue failure”, characterized by dysregulation of adipokine production, has been implicated in the pathophysiology of these metabolic complications. Adiponectin, an insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic adipokine, circulates in oligomeric complexes including: low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms. These multimers exert differential biological effects, and HMW to total adiponectin ratio (SA) has been reported to be a specific marker of adiponectin activity. The aim of this study was to determine whether preeclampsia is associated with changes in circulating adiponectin multimers. Study design This cross-sectional study included women with: 1) normal pregnancy (n=225); and 2) patients with mild preeclampsia (n=111). The study population was further stratified by first trimester BMI (normal weight <25 kg/m2 vs. overweight/obese ≥25 kg/m2). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results 1) The median maternal HMW and LMW adiponectin concentrations were lower in patients with preeclampsia than in those with normal pregnancies (p<0.001 and p=0.01, respectively); 2) patients with preeclampsia had a lower HMW/Total adiponectin ratio (p<0.001) and higher MMW/Total adiponectin and LMW/Total adiponectin ratios than those with a normal pregnancy (p<0.001 and p=0.009, respectively); 3) the presence of preeclampsia was independently associated with lower maternal serum HMW adiponectin concentrations (p=0.001) and with a low HMW/Total adiponectin ratio (p<0.001) after correction for maternal age, maternal BMI, the difference in BMI between the third and the first trimester, and gestational age at sampling; and 4) overweight/obese pregnant women had a lower median total and HMW adiponectin concentration than normal weight pregnant women among women with normal pregnancies, but not among those with preeclampsia. Conclusion 1) Preeclampsia is associated with a lower median concentration of the HMW adiponectin isoform, the most active form of this adipokine, and a low HMW/Total adiponectin ratio, a specific marker of adiponectin biologic activity; 2) in contrast to normal pregnancy, preeclampsia is not associated with decreased circulating adiponectin multimers in overweight/obese individuals suggesting altered regulation of this adipokine in preeclampsia; 3) collectively, these findings suggest that preeclampsia is characterized by alterations in adiponectin multimers and their relative distribution implying a role for adiponectin multimers in the mechanism of disease in preeclampsia.

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“…An increase toward mid-pregnancy and a decrease thereafter or inversely, a mid-gestational trough has been described [23] . In women with PE, the scarcity of data does not allow a sound conclusion regarding its variation, but sRAGE levels appear to be increased [24] .…”

Section: Discussionmentioning

confidence: 99%

“…Clearly, further studies are needed to provide clarification on these issues. Another study showed that the increasing levels of esRAGE in women with PE did not persist at 6 months after delivery [35] . Therefore, we support the view that the variations in sRAGE levels in both maternal blood and umbilical cord blood are rather an effect of PE than a cause of the disease.…”

Section: Discussionmentioning

confidence: 99%

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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Endogenous soluble receptor for advanced glycation endproducts is increased in preeclampsia

Abstract: We showed that maternal esRAGE concentrations are significantly increased in patients with preeclampsia during pregnancy. Here, insulin sensitivity and inflammatory status independently predict serum esRAGE levels.

Cited by 10 publications

References 18 publications

Reduced soluble receptor for advanced glycation end‐products (sRAGE) scavenger capacity precedes pre‐eclampsia in Type 1 diabetes

Reduced soluble receptor for advanced glycation end‐products (sRAGE) scavenger capacity precedes pre‐eclampsia in Type 1 diabetes

Maternal serum adiponectin multimers in preeclampsia

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

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