scholarly journals Soluble Receptor for Advanced Glycation End Products (sRAGE) Is a Sensitive Biomarker in Human Pulmonary Arterial Hypertension

2021 ◽  
Vol 22 (16) ◽  
pp. 8591
Author(s):  
Franziska Diekmann ◽  
Philippe Chouvarine ◽  
Hannes Sallmon ◽  
Louisa Meyer-Kobbe ◽  
Moritz Kieslich ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Advanced Glycation End Products ◽  
Unmet Need ◽  
Advanced Glycation ◽  
Characteristic Analysis ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a progressive condition with an unmet need for early diagnosis, better monitoring, and risk stratification. The receptor for advanced glycation end products (RAGE) is activated in response to hypoxia and vascular injury, and is associated with inflammation, cell proliferation and migration in PAH. For the adult cohort, we recruited 120 patients with PAH, 83 with idiopathic PAH (IPAH) and 37 with connective tissue disease-associated PAH (CTD-PAH), and 48 controls, and determined potential plasma biomarkers by enzyme-linked immunoassay. The established heart failure marker NTproBNP and IL-6 plasma levels were several-fold higher in both adult IPAH and CTD-PAH patients versus controls. Plasma soluble RAGE (sRAGE) was elevated in IPAH patients (3044 ± 215.2 pg/mL) and was even higher in CTD-PAH patients (3332 ± 321.6 pg/mL) versus controls (1766 ± 121.9 pg/mL; p < 0.01). All three markers were increased in WHO functional class II+III PAH versus controls (p < 0.001). Receiver-operating characteristic analysis revealed that sRAGE has diagnostic accuracy comparable to prognostic NTproBNP, and even outperforms NTproBNP in the distinction of PAH FC I from controls. Lung tissue RAGE expression was increased in IPAH versus controls (mRNA) and was located predominantly in the PA intima, media, and inflammatory cells in the perivascular space (immunohistochemistry). In the pediatric cohort, plasma sRAGE concentrations were higher than in adults, but were similar in PH (n = 10) and non-PH controls (n = 10). Taken together, in the largest adult sRAGE PAH study to date, we identify plasma sRAGE as a sensitive and accurate PAH biomarker with better performance than NTproBNP in the distinction of mild PAH from controls.

Soluble RAGE Sequesters Advanced Glycation End Products following an Overnight Fast in T1DM Patients

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 275-LB
Author(s):  
EDWIN R. MIRANDA ◽  
JR. KELLY N. FULLER ◽  
RYAN PERKINS ◽  
PAUL J. BEISSWENGER ◽  
SARAH S. FARABI ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

scholarly journals Proteolytic release of the receptor for advanced glycation end products from in vitro and in situ alveolar epithelial cells

2011 ◽  
Vol 300 (4) ◽  
pp. L516-L525 ◽  
Author(s):  
Naoko Yamakawa ◽  
Tokujiro Uchida ◽  
Michael A. Matthay ◽  
Koshi Makita
Keyword(s):  
Epithelial Cells ◽  
Advanced Glycation End Products ◽  
Alveolar Epithelial Cells ◽  
Advanced Glycation ◽  
Alveolar Epithelial ◽  
Lps Challenge ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

Although the receptor for advanced glycation end products (RAGE) has been used as a biological marker of alveolar epithelial cell injury in clinical studies, the mechanism for release of soluble RAGE from lung epithelial cells has not been well studied. Therefore, these studies were designed to determine the mechanism for release of soluble RAGE after lipopolysaccharide (LPS) challenge. For these purposes, alveolar epithelial cells from rat lungs were cultured on Transwell inserts, and LPS was added to the apical side (500 μg/ml) for 16 h on day 7. On day 7, RAGE was expressed predominantly in surfactant protein D-negative cells, and LPS challenge induced release of RAGE into the medium. This response was partially blocked by matrix metalloproteinase (MMP) inhibitors. Transcripts of MMP-3 and MMP-13 were upregulated by LPS, whereas RAGE transcripts did not change. Proteolysis by MMP-3 and MMP-13 resulted in soluble RAGE expression in the bronchoalveolar lavage fluid in the in situ rat lung, and this reaction was inhibited by MMP inhibitors. In human studies, both MMP-3 and -13 antigen levels were significantly correlated with the level of RAGE in pulmonary edema fluid samples. These results support the conclusion that release of RAGE is primarily mediated by proteolytic damage in alveolar epithelial cells in the lung, caused by proteases in acute inflammatory conditions in the distal air spaces.

scholarly journals Association of the Receptor for Advanced Glycation End Products Gene Polymorphisms and Circulating RAGE Levels with Diabetic Retinopathy in the Chinese Population

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Li Yang ◽  
Qunhong Wu ◽  
Yuan Li ◽  
Xiaohong Fan ◽  
Yanhua Hao ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Chinese Population ◽  
Genetic Interaction ◽  
Interaction Model ◽  
Serum Levels ◽  
Advanced Glycation ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

Objectives. This study investigated the association between polymorphisms in the receptor for advanced glycation end products (RAGE) gene and the susceptibility to diabetic retinopathy (DR) in a Chinese population and identified a correlation between serum-soluble RAGE (sRAGE) levels and DR risk.Materials and Methods. We enrolled 1040 patients with type 2 diabetes mellitus: 372 patients with DR and 668 without retinopathy (NDR). All polymorphisms were genotyped by time-of-flight mass spectrometry. Serum levels of sRAGE were assayed by enzyme-linked immunosorbent assays. The interaction of SNPs was analyzed by multifactor dimensionality reduction (MDR).Results. The frequency of the SS genotype for the G82S polymorphism was 12.4% in the DR group and 6.6% in the NDR group; this difference was significant. G82S was associated with sRAGE levels. Specifically, after adjustments for age, sex, duration, and glucose metabolism, serum sRAGE levels were significantly higher in DR subjects with the S/S genotype than in NDR subjects in general. In the DR group, subjects with the G/S genotype had lower sRAGE levels than subjects with the G/G or S/S genotype (P<0.01). The best multilocus genetic interaction model was assessed using the MDR method; 2184A/G, 1704G/T, G82S, and −429T/C were identified.Conclusions. The findings suggest that the G82S polymorphism in theRAGEgene is associated with DR risk, and G82S was associated with circulating levels of sRAGE. The mechanism by which G82S polymorphism modulates the sRAGE levels remains to be elucidated.

ID: 83: PRODUCTION OF SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END-PRODUCTS FOLLOWING ACUTE AEROBIC EXERCISE IS GENDER SPECIFIC

2016 ◽  
Vol 64 (4) ◽  
pp. 928.2-929
Author(s):  
ER Miranda ◽  
JT Mey ◽  
BK Blackburn ◽  
JM Haus ◽  
SS Farabi ◽  
...  
Keyword(s):  
Aerobic Exercise ◽  
Advanced Glycation End Products ◽  
Acute Exercise ◽  
Primary Objective ◽  
Advanced Glycation ◽  
Insulin Resistant ◽  
Soluble Rage ◽  
Downstream Effectors ◽  
Glycation End Products ◽  
End Products

The Receptor for Advanced Glycation End Products (RAGE) is a transmembrane receptor that initiates a self-propagating inflammatory cascade and has been implicated in the onset of complications involved with aging, diabetes and neuroinflammation. Soluble RAGE (sRAGE) inhibits this inflammatory signaling by competitively binding to RAGE ligands without stimulating downstream effectors. Evidence from our lab demonstrates chronic aerobic exercise increases the cleaved isoform of sRAGE (sRAGEc). However, the effects of acute aerobic exercise on sRAGEc production have not been comprehensively examined. Furthermore, recent data suggests that estrogen may play a role in exacerbating RAGE signaling and perturbing sRAGE production in diabetic women. Therefore, the primary objective of this study was to investigate changes in plasma sRAGE with acute aerobic exercise in both lean healthy (LH) and obese insulin resistant (OB-IR) individuals. A secondary objective of the study was to compare exercise responses between men and women. 8 LH participants (4 M, 4 F) and 14 OB-IR participants (4 M, 10 F) were recruited for the study. VO2max was determined via treadmill test and participants returned to the lab on a separate day following an overnight fast and exercised at 65% VO2max for 30 minutes. Blood samples were collected before and following exercise after participants rested in seated position for 30 minutes. Quantification of plasma sRAGE and endogeonous secretory RAGE were determined via ELISA and sRAGEc was calculated by subtraction. Between-group comparisons were made via independent T Test and the effect of gender was analyzed via two-way ANOVA. At baseline the OB-IR group was older (41±3 y vs. 26±1 y, p<.001), more obese (BMI 35.1±0.9 vs. 22.2±0.9 kg . m−2, p<.001) and less aerobically fit (VO2max 27.8±1.8 vs. 50.2±2.9 mL/kg−1. min−1, p<.001) compared the LH group. There was no main effect of group (OB-IR vs. LHC) on change in sRAGE or sRAGEc in response to exercise (ΔsRAGE 20.3±53.2 vs. 13.8±34.4 pg/mL, p=.93), (ΔsRAGEc 28.7±47.1 vs. 14.4±34.8 pg/mL, p=.33). However there was an effect of gender on the response to acute exercise. Males in both groups saw a significantly greater increase in plasma sRAGE (131.49±46.46 vs. −46.94±39.23 pg/mL, p<.05) and plasma sRAGEc (127.73±47.04 vs. −36.08±34.13 pg/mL, p<.05) compared to females. This study is the first to show that young healthy women and obese/insulin resistant women have an impaired ability to increase sRAGE plasma levels with acute aerobic exercise. Recent data has suggested that estrogen can exacerbate RAGE signaling as well as inhibit sRAGE production although the precise mechanism for this interaction is unclear and warrants further investigation.

scholarly journals Ligands of RAGE-Proteins: Role in Intercellular Communication and Pathogenesis of Inflammation

2015 ◽  
Vol 70 (6) ◽  
pp. 694-703 ◽  
Author(s):  
Yuliya Aleksandrovna Uspenskaya ◽  
Yuliya Konstantinovna Komleva ◽  
Elena Anatol'evna Pozhilenkova ◽  
Vladimir Valer'evic Salmin ◽  
Ol'ga Leonidovna Lopatina ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Advanced Glycation End Products ◽  
Calcium Binding ◽  
Advanced Glycation ◽  
Endogenous Ligands ◽  
Inflammatory Reactions ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

The review contains data on the diversity of endogenous ligands of RAGE receptors (receptor for advanced glycation end products) that play an important role in the signal transduction in (patho) physiological conditions. RAGE takes part in various physiological processes like cell growth and survival, apoptosis and regeneration. They serve as regulators of inflammatory reactions due to their ability to induce secretion of cytokines and chemokines. In addition, they facilitate elimination of apoptotic cells and mediate innate immune response. We discuss mechanisms of soluble RAGE production as well as the role of membrane and soluble forms of the receptor in cell signaling. Several endogenous ligands of RAGE are well-known: advanced glycation end products (AGE), amyloid-beta (Аβ), nuclear high mobility group box 1 proteins (HMGB1), and calcium-binding proteins S100A4, S100A8/A9, S100A12 и S100B. The review is focused on the mechanisms of the ligands production, their secretion from the cells of various origin, interaction with RAGE, and associated intracellular signal transduction pathways. Special attention is paid to the role of RAGE in pathogenesis of inflammation, particularly, in brain injury and neurodegeneration.

scholarly journals Leptin and advanced glycation end products receptor (RAGE) in tuberculosis patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254198
Author(s):  
Tássia Kirchmann Lazzari ◽  
Erika Cavalheiro ◽  
Sandra Eugênia Coutinho ◽  
Lívia Fontes da Silva ◽  
Denise Rossato Silva
Keyword(s):  
Weight Loss ◽  
Advanced Glycation End Products ◽  
Inverse Correlation ◽  
Advanced Glycation ◽  
Serum Leptin ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products ◽  
Carboxymethyl Lysine ◽  
Control Study

Introduction The pathogenesis of consumptive syndrome of tuberculosis (TB) is largely unknown. Leptin concentrations may be high because of the host’s inflammatory response, contributing to weight loss in patients with TB. The receptor for advanced glycation end products (RAGE) is also associated with weight loss in patients with TB and is related to enhanced mortality. The objective of this study was to evaluate the association between leptin and AGE/RAGE. Methods Case-control study. Leptin, AGE (carboxymethyl lysine, CML) and soluble RAGE (sRAGE) were measured from blood samples by ELISA. Results We included in the study 34 patients with TB and 34 controls. We found an inverse correlation between serum leptin levels and sRAGE, only in cases (r = -0.609, p < 0.0001). sRAGE levels were lower in patients with TB who died as compared with patients who survive (21.90 ± 4.24 pg/mL vs 66.14 ± 29.49 pg/mL; p = 0.045). Leptin levels were higher in patients with TB who died as compared with patients who survive (14.11 [7.48–14.11] ng/mL vs 3.08 [0.54–6.34] ng/mL; p = 0.028). Conclusions We identified lower sRAGE levels and higher leptin levels in patients with TB who died as compared with patients who survive. In addition, an inverse and significant correlation between serum leptin and sRAGE levels was demonstrated. Future studies, with a larger sample size and in different settings, including not only hospitalized patients, are needed to confirm these findings.

scholarly journals Receptor of advanced glycation end products and cardiovascular risk in elderly with type 2 diabetes mellitus

2018 ◽  
Vol 90 (2) ◽  
Author(s):  
Claudia Borsa ◽  
Daniela Gradinaru ◽  
Denisa Margina ◽  
Gabriel Ioan Prada ◽  
Catalina Pena
Keyword(s):  
Cardiovascular Risk ◽  
Advanced Glycation End Products ◽  
Vascular Complications ◽  
Elderly Subjects ◽  
Risk Markers ◽  
Advanced Glycation ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

The interaction of Advanced Glycation End products (AGEs) and their specific receptor, Receptor for Advanced Glycation End products (RAGE) play an important role in diabetes and vascular complications. Engagement of RAGE by AGEs leads to activation of cellular signaling pathways and vascular dysfunction. The soluble RAGE (sRAGE) acts as a decoy receptor for AGEs. The aim of this study was to evaluate the soluble RAGE in elderly subjects with T2DM and its relationships with glycoxidative, inflammatory and cardiovascular risk markers. The serum AGEs, sRAGE, interleukine- 6 (IL-6), lipid profile, glycemic status, uric acid, creatinine and cardiovascular risk markers were determined in elderly subjects with type 2 diabetes mellitus (T2DM, N=72, 75±4 years old) and aged-match healthy subjects (N=15, 76±3 years old). Significant higher levels of AGEs and AGEs/sRAGE ratio concomitantly with significant lower levels of sRAGE were pointed out in elderly subjects with T2DM as compared to control. The values of AGEs/sRAGE ratio were significantly positively associated (P<0.05) with atherogenic, inflammatory and cardiovascular risk markers and significantly negatively with anti-atherogenic lipoproteins (P<0.05). The multivariate regression analyses showed that atherogenic index was an independent predictor of sRAGE levels and AGEs/sRAGE ratio values. The associations of soluble RAGE and the AGEs/sRAGE ratio with atherogenic and inflammatory markers could reflect the protective role of soluble variants of RAGE in atherosclerosis and diabetes vascular complications.

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