Soluble receptor for advanced glycation end-products positively correlated to kidney injury with coronary heart disease.

AIMS: Coronary heart disease (CHD) patients with changed serum soluble receptor for advanced glycation end products (sRAGE) will experience microalbuminuria and even kidney dysfunction. However, the role of sRAGE for microalbuminuria in CHD is still not established. This study aimed to evaluate the association between sRAGE and early kidney dysfunction in CHD patients. MATERIALS AND METHODS: In this cross-sectional study, sRAGE and urinary albumin-to-creatinine ratio (uACR) were measured in hospitalized CHD patients who have undergone coronary arteriography to evaluate the distinction and correlation between sRAGE and uACR. RESULTS: There were 127 CHD patients (mean age: 63.06 ± 10.93 years, 93 males) in the study, whose sRAGE were 1.83 ± 0.64 µg/L. The sRAGE level was higher in kidney injury group (uACR ≥ 30 mg/g) compared with no kidney injury group (uACR < 30 mg/g) [(2.08 ± 0.70 vs. 1.75 ± 0.61) µg/L, P < 0.05]. Moreover, the positive correlation between serum sRAGE and uACR was significant in CHD patients (r = 0.196, P < 0.05). Binary logistic regression suggests sRAGE as a predictor for microalbuminuria in CHD patients [Odd Ratio = 2.62 (1.12-6.15), P < 0.05)]. The area under the receiver operating characteristic curve (AUC) of sRAGE is higher than that of the traditional indicators of renal function such as creatinine and estimated glomerular filtration rate, indicating sRAGE might have a good performance in evaluating early kidney injury in CHD patients [AUC is 0.660 (0.543-0.778), P < 0.01)]. CONCLUSIONS: Serum sRAGE was positively correlated to uACR and might serve as a potential marker to predict early kidney injury in CHD patients.

Correlation between circulating advanced glycation end products and thioredoxin-interacting protein levels and renal fat content in type 2 diabetes mellitus patients.

BACKGROUND: This study sought to explore the clinical relevance of the associations of serum levels of advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), and thioredoxin-interacting protein (TXNIP) with the renal fat fraction (RFF) in individuals with type 2 diabetes mellitus (T2DM). METHODS: A total of 133 patients with T2DM were enrolled in the study. RFF, which represents the renal fat level, was determined utilizing Dixon magnetic resonance imaging (MRI). Serum levels of AGEs, sRAGE, TXNIP, and other biochemical parameters were measured in patients who fasted. RESULTS: RFF in T2DM patients was positively correlated with the fasting levels of C-peptide (CP), triglycerides (TG), AGEs, TXNIP, and sRAGE (P < 0.05) and negatively correlated with the high-density lipoprotein cholesterol (HDL-c) level (P < 0.05). Pearson's correlation analysis indicated that the serum levels of AGEs, sRAGE, and TXNIP were interrelated and positively correlated (P < 0.05). Then, all patients were assigned to four groups according to the RFF quartile. The HC, CP, TG, AGEs, sRAGE, TXNIP, and DKD percentages tended to increase as the RFF quartiles increased, while the HDL-c level tended to decrease (p for trend < 0.05). Next, multiple linear regression analysis was performed using RFF as the dependent variable. After controlling for covariates related to RFF, the results showed that the serum levels of AGEs and TXNIP were still significantly correlated with RFF. CONCLUSION: These results suggest that circulating AGEs and TXNIP levels may be associated with ectopic fat accumulation in the kidneys of T2DM patients and may serve as indicators of the severity of renal fat deposition.

Effects of dried okra extract on lipid profile, renal function and some RAGE-related inflammatory genes expression in patients with diabetic nephropathy: A randomized controlled trial.

BACKGROUND: Diabetic nephropathy (DN) is a common complication of type 2 diabetes. Okra (Abelmoschus esculentus L) is reported to have anti-diabetic effects. The present study aimed to investigate the effects of dried okra extract (DOE) supplementation on lipid profile, renal function indices, and expression of inflammatory genes, as well as serum level of soluble Receptor for Advanced glycation end products (sRAGE) in patients with DN. METHODS: In this triple-blind randomized placebo-controlled clinical trial, 64 eligible patients with DN received either 125 mg of DOE or placebo daily along with DN-related nutritional recommendations for 10 weeks. Changes in kidney indices including proteinuria and estimated glomerular filtration rate (eGFR), lipid profile, serum SRAGE, as well as the expression of RAGE, ICAM-1, and IL-1 genes were measured over 10 weeks. RESULTS: After adjustment for the potential confounders, between-group analyses showed no significant differences in terms of lipid profile, kidney function indices, sRAGE, and RAGE-related inflammatory genes expression after 10 weeks. CONCLUSION: Daily 125 mg DOE along with nutritional recommendations on top of usual care did not lead to significant changes in renal function indices, lipid profile, and inflammatory genes expression in patients with DN.

Association of four differently processed diets with plasma and urine advanced glycation end products and serum soluble receptor for advanced glycation end products concentration in healthy dogs.

Advanced glycation end products (AGEs), formed via the Maillard reaction (MR) during processing of foods, have been implicated in inflammatory and degenerative diseases in human beings. Cellular damage is primarily caused by AGE binding with the receptor for AGEs (RAGE) on cell membranes. An isoform of RAGE, soluble RAGE (sRAGE), acts as a decoy receptor binding circulating AGEs preventing cellular activation. Pet food manufacturing involves processing methods similar to human food processing that may increase dietary AGEs (dAGEs). We hypothesized that diet, plasma and urine AGEs, and serum sRAGE concentrations would differ between thermally processed diets. This study examined the association of four differently processed diets: ultra-processed canned wet food (WF); ultra-processed dry food (DF); moderately processed air-dried food (ADF) and minimally processed mildly cooked food (MF) on total plasma levels of the AGEs, carboxymethyllysine (CML), carboxyethyllysine (CEL), methylglyoxal hydroimidazolone-1, glyoxal hydroimidazolone-1, argpyrimidine, urine CML, CEL and lysinoalanine, and serum sRAGE concentration. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure AGEs. sRAGE concentration was measured using a commercial canine-specific enzyme-linked immunosorbent assay kit. Total dAGEs (mg/100 kcal as fed) were higher in WF than in other diets. Plasma total AGEs (nM/50 µL) were significantly higher with WF, with no difference found between DF, ADF, and MF; however, ADF was significantly higher than MF. Urine CML (nmol AGEs/mmol creatinine) was significantly higher with DF than with WF and MF. There were no significant differences in total urine AGEs or serum sRAGE concentration between diets. In conclusion, different methods of processing pet foods are associated with varied quantities of AGEs influencing total plasma AGE concentration in healthy dogs. Serum sRAGE concentration did not vary across diets but differences in total AGE/sRAGE ratio were observed between MF and WF and, ADF and DF.

Biomarkers of Oxidative Stress in Systemic Lupus Erythematosus Patients with Active Nephritis.

Oxidative stress plays an important role in systemic lupus erythematosus (SLE) and especially in lupus nephritis (LN). The aim of this study was to compare redox-related biomarkers between patients with active LN, quiescent SLE (Q-SLE) and healthy controls (HC) and to explore their association with clinical characteristics such as disease activity in patients. We investigated levels of plasma free thiols (R-SH, sulfhydryl groups), levels of soluble receptor for advanced glycation end products (sRAGE) and levels of malondialdehyde (MDA) in SLE patients with active LN (n = 23), patients with quiescent SLE (n = 47) and HC (n = 23). Data of LN patients who previously participated in Dutch lupus nephritis studies and longitudinal samples up to 36 months were analyzed. Thiol levels were lower in active LN at baseline and Q-SLE patients compared to HC. In generalized estimating equation (GEE) modelling, free thiol levels were negatively correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) over time (p < 0.001). sRAGE and MDA were positively correlated with the SLEDAI over time (p = 0.035 and p = 0.016, respectively). These results indicate that oxidative stress levels in LN patients are increased compared to HC and associated with SLE disease activity. Therefore, interventional therapy to restore redox homeostasis may be useful as an adjunctive therapy in the treatment of oxidative damage in SLE.

Genetically Modified Circulating Levels of Advanced Glycation End-Products and Their Soluble Receptor (AGEs-RAGE Axis) with Risk and Mortality of Breast Cancer.

The interaction of advanced glycation end-products (AGEs) with their receptor (RAGE) elicits oxidative stress and inflammation, which is involved in the development of breast cancer. However, large-scale population-based evidence exploring genetically modified circulating levels of AGEs-RAGE axis with risk and mortality of breast cancer is scarce. We recruited 1051 pairs of age-matched breast cancers and controls and measured plasma AGEs and sRAGE concentrations by enzyme-linked immunosorbent assay (ELISA). Multivariate logistic regression and Cox proportional hazard model were used to calculate the effects of plasma levels and genetic variants of the AGEs-RAGE axis and their combined effects on breast cancer risk and prognosis, respectively. Furthermore, linear regression was performed to assess the modifications in plasma AGEs/sRAGE levels by genetic predisposition. Higher levels of AGEs and AGEs/sRAGE-ratio were associated with an increased risk of breast cancer, but sRAGE levels were negatively associated with breast cancer risk, especially in women <60 years. We also observed a positive association between AGEs and the bad prognosis of breast cancer. Although we did not observe a significant contribution of genetic variants to breast cancer risk, rs2070600 and rs1800624 in the AGER gene were dose-dependently correlated with sRAGE levels. Further, compared to the haplotype CT at the lowest quartile of AGEs, haplotypes TT and TA were prominently associated with breast cancer risk in the highest quartile of AGEs. This study depicted a significant association between circulating levels of AGEs-RAGE axis and breast cancer risk and mortality and revealed the potential of plasma AGEs, especially coupled with AGER polymorphism as biomarkers of breast cancer.

Altered expression of a disintegrin and metalloproteinase 10 in peripheral blood mononuclear cells in type 2 diabetes mellitus patients with the acute coronary syndrome: a pilot study.

PURPOSE: Advanced glycation end products (AGEs) are responsible for the complications in type 2 diabetes mellitus (T2DM) patients by acting via its receptor (RAGE). The soluble form of RAGE (sRAGE) prevents the harmful effects of AGE-RAGE signalling. The sRAGE is produced either by alternate splicing (esRAGE) or proteolytic RAGE cleavage by a disintegrin and metalloproteinase 10 (ADAM10). Hence, the study aimed to compare the expression of ADAM10 in peripheral blood mononuclear cell (PBMC), serum sRAGE and esRAGE levels in T2DM patients with and without acute coronary syndrome (ACS). METHODS: Forty-five T2DM patients with ACS and 45 age, gender and duration of DM-matched T2DM patients without ACS were recruited. Serum sRAGE and esRAGE levels were measured by enzyme-linked immunosorbent assay. The expression of ADAM10 in PBMC was determined by quantitative reverse transcription-polymerase chain reaction. RESULTS: The expression of ADAM10 in PBMC and serum sRAGE levels were significantly lower in T2DM patients with ACS than in T2DM patients without ACS (p < 0.001). Serum sRAGE levels and expression of ADAM10 in PBMC were positively correlated with each other and negatively correlated with markers of cardiac injury and glycaemic status (p < 0.05). Simple logistic regression showed that the models containing the expression of ADAM10 and serum sRAGE level could predict the ACS risk among T2DM patients. ROC analysis showed that both might be used for ACS diagnosis in T2DM patients. CONCLUSION: Reduced expression of ADAM10 in PBMC might be responsible for lower serum sRAGE levels, predisposing T2DM patients to high ACS risk.

[The Value of Serum HMGB1 and sRAGE in the Diagnosis, Efficacy Monitoring and Prognosis of Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To evaluate the value of high mobility group protein B1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the diagnosis, efficacy monitoring and prognosis of newly diagnosed multiple myeloma (MM) patients. METHODS: Fifty newly diagnosed MM patients before and after chemotherapy and 50 hematological outpatients from October 2018 to May 2020 were selected. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum HMGB1 and sRAGE levels of the patients. ROC was used to further analyze the efficacy of serum HMGB1 and sRAGE levels on the diagnosis of MM. At the same time, the serum levels of HMGB1 and sRAGE before and after chemotherapy were compared, and their values in the evaluation of curative effect of MM patients were analyzed. According to the mean values of serum HMGB1 and sRAGE, all the patients were divided into different groups, the clinical characteristics and survival status of the patients were compared. RESULTS: Before treatment the serum HMGB1 level of the patients in MM group was higher than that in control group, while sRAGE level was lower (t=11.363,6.127, P<0.001). The AUC of serum HMGB1 and sRAGE in the MM patients was 0.955 and 0.811, respectively. After 3 courses of chemotherapy, HMGB1 level of the patients in CR group was lower than before chemotherapy, while in PD group was higher, as well as sRAGE level of the patients in PR group (P<0.05). There were significant differences in R-ISS stage, HGB, CRP, ESR, CD56, CD117, D13S319 deletion between HMGB1 high expression group and HMGB1 low expression group (χ2=3.920, 6.522, 6.65, 4.16, 3.945, 6.65, 4.16, P<0.05), while there were significant differences in ISS stage, CRP and CD56 between sRAGE low expression group (28 cases) and sRAGE high expression group (22 cases) (χ2=4.565, 4.711, 5.547, P<0.05). Kaplan-Meier survival analysis showed that the patients in HMGB1 low expression group had better survival condition, for PFS Tlow>Thigh (χ2=9.470, P<0.05), and for OS Tlow>Thigh (χ2=7.808, P<0.05); there was no difference in the survival of sRAGE high expression group and low expression group, for PFS Tlow0.05), and for OS Tlow0.05). Cox analysis showed that LDH and HMGB1 were the factors affecting the prognosis of the patients, and both of them affected PFS (HR=2.771, 95% CI: 1.002-7.662, P=0.049; HR=6.022, 95% CI: 1.689-21.470, P=0.006), while HMGB1 also affected OS (HR=4.275, 95% CI: 1.183-15.451, P=0.027). CONCLUSION: The serum HMGB1 and sRAGE have certain auxiliary value for the diagnosis and curative effect monitoring of newly diagnosed MM patients, and serum HMGB1 is expected to be an auxiliary detection index for the prognosis of MM.

Integrinß3 mediates the protective effects of soluble receptor for advanced glycation end-products during myocardial ischemia/reperfusion through AKT/STAT3 signaling pathway.

Soluble receptor for advanced glycation end-product (sRAGE) was reported to protect myocardial ischemia/reperfusion (I/R) injuries via directly interacting with cardiomyocytes besides competing with RAGE for AGEs. However, the specific molecule for the interaction between sRAGE and cardiomyocytes are not clearly defined. Integrins which were reported to interact with RAGE on leukocytes were also expressed on myocardial cells, therefore it was supposed that sRAGE might interact with integrins on cardiomyocytes to protect hearts from ischemia/reperfusion injuries. The results showed that sRAGE increased the expression of integrinß3 but not integrinß1, ß2, ß4 or ß5 in cardiomyocytes during I/R injuries. Meanwhile, the suppressive effects of sRAGE on cardiac function, cardiac infraction size and apoptosis in mice were cancelled by inhibition of integrinß3 with cilengitide (CLG, 75 mg/kg). The results from cultured cardiomyocytes also proved that sRAGE attenuated myocardial apoptosis and autophagy through interacting with integrinß3 to activate Akt and STAT3 pathway during oxygen and glucose deprivation/reperfusion (OGD/R) treatment. Furthermore, the phosphorylation of STAT3 was significantly downregulated by the inhibition of Akt (LY294002, 10 µM) in OGD/R and sRAGE treated cardiomyocytes, which suggested that STAT3 pathway was induced by Akt in I/R and sRAGE treated cardiomyocytes. The present study contributes to the understanding of myocardial I/R pathogenesis and provided a novel integrinß3-dependent therapy strategy for sRAGE ameliorating I/R injuries.

SERUM CARBOXYMETHYL-LYSINE AND SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS IN HYPERTHYROID AND HYPOTHYROID PATIENTS.

Purpose: The formation and accumulation of advanced glycation end products (AGEs) are enhanced with increased oxidative stress and inflammatory conditions. A hyperthyroid and hypothyroid state is associated with oxidative stress. This study aimed to evaluate skin AGE deposition, serum carboxymethyl-lysine (CML), and serum soluble receptor for AGEs (sRAGE) levels in hypothyroid and hyperthyroid patients. Methods: A total of 203 subjects were included in this cross-sectional study. After excluding diabetes mellitus, 103 newly diagnosed hypothyroid patients, 50 newly diagnosed hyperthyroid patients, and 50 control (euthyroid) subjects were enrolled. All tests were done before beginning the appropriate treatment. Accumulated AGEs in the skin collagen were measured by skin autofluorescence (SAF) using an AGE Reader. Results: SAF measurements were 1.82 ± 0.04, 1.80 ± 0.40, and 1.63 ± 0.30 arbitrary units for the hypothyroid, hyperthyroid, and euthyroid groups, respectively (p = 0.04). Serum CML levels were 8.2 ± 2.8, 10.2 ± 2.0, and 8.0 ± 3.3 ng/mL for the hypothyroid, hyperthyroid, and euthyroid groups, respectively (p = 0.01). sRAGE levels were similar between the groups. Serum thyroid-stimulating hormone and SAF measurements were positively correlated (r = 0.25, p = 0.02) in the hypothyroid group and negatively correlated in the hyperthyroid group (r = -0.36, p = 0.04). There was no correlation between CML and sRAGE levels. Conclusion: SAF measurements are increased in both hypo- and hyperthyroid normoglycemic patients. Serum CML levels are increased in hyperthyroid patients. Hypo and hyperthyroid states might be associated with acceleration of AGE accumulation and may have a long term effect on metabolic memory.

Does dietary fat affect advanced glycation end products and their receptors? A systematic review of clinical trials.

CONTEXT: Dietary fat seems to affect advanced glycation end products (AGEs) and their receptors. This systematic review assesses studies that evaluated the effect of dietary fat on markers of glycation. OBJECTIVE: The aim of this systematic review was to analyze the effect of dietary fat on markers of glycation and to explore the mechanisms involved. DATA SOURCES: This study was conducted according to PRISMA guidelines. PubMed, Cochrane, and Scopus databases were searched, using descriptors related to dietary fat, AGEs, and the receptors for AGEs. STUDY SELECTION: Studies were selected independently by the 3 authors. Divergent decisions were resolved by consensus. All studies that evaluated the effects of the quantity and quality of dietary fat on circulating concentrations of AGEs and their receptors in adults and elderly adults with or without chronic diseases were included. Initially, 9 studies met the selection criteria. DATA EXTRACTION: Three authors performed data extraction independently. Six studies were included. RESULTS: Consumption of a Mediterranean diet rich in monounsaturated fatty acids (MUFAs) and low in dietary AGEs reduced serum concentrations of AGEs, reduced expression of the receptor for AGE (RAGE), and increased expression of the AGE receptor 1 (AGER1) when compared with consumption of a Western diet rich in saturated fatty acids and dietary AGEs. Supplementation with omega-3 polyunsaturated fatty acids (PUFAs) resulted in decreased concentrations of fluorescent AGEs and decreased expression of RAGE as well as increased expression of AGER1. CONCLUSIONS: Increased consumption of MUFAs and omega-3 PUFAs and reduced consumption of saturated fatty acids seem to be effective strategies to beneficially affect glycation markers, which in turn may prevent and control chronic diseases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42021220489.

Hemodialysis Patients with Higher Serum Levels of Soluble Receptor for Advanced Glycation End Products Have an Increased Risk for Arteriovenous Fistula Failure.

BACKGROUND: Arteriovenous fistula (AVF) failure due to thrombosis is a major cause of morbidity in patients undergoing regular hemodialysis (HD). Advanced glycation end products (AGEs) and their receptor (RAGE) might contribute to inflammation, neointimal hyperplasia, and thrombosis. RAGE has a C-truncated secretory receptor form, called soluble RAGE (sRAGE). In this study, we aimed to evaluate the association of serum sRAGE with AVF failure due to thrombosis in HD patients. METHODS: Eighty-eight prevalent HD patients with functional AVF were included in the study. The presence of stenosis, clinical and laboratory data, and serum sRAGE was evaluated at inclusion. sRAGE concentration was measured by a competitive enzyme-linked immunosorbent assay, and stenosis was detected by ultrasound. Patients were prospectively followed up for 36 months. During this period, AVF failure (defined as the absence of blast or palpable thrill and impossible cannulation with 2 needles because of complete thrombosis) was noted and thrombosis was certified by ultrasound examination. RESULTS: During follow-up, 16 (18.18%) patients lost their vascular access due to thrombosis. In multivariate Cox regression analysis, sRAGE was a significant predictor of vascular access thrombosis (hazard ratio = 1.15, 95% confidence interval: 1.03-1.25, p = 0.012). Kaplan-Meier analysis showed a significantly lower AVF patency time in patients with sRAGE >16.78 ng/mL than those with sRAGE <16.78 ng/mL (p = 0.02). In the subgroup of patients with stenosis at baseline, sRAGE, serum albumin, obesity, and ischemic heart disease were associated with thrombosis. CONCLUSION: In our study, baseline, systemic sRAGE is associated with the occurrence of thrombosis of AVF, and this marker has a significant impact on AVF survival.

Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury.

The full-length receptor for advanced glycation end products (RAGE) is a multiligand pattern recognition receptor. High-mobility group box 1 (HMGB1) is a RAGE ligand of damage-associated molecular patterns that elicits inflammatory reactions. The shedded isoform of RAGE and endogenous secretory RAGE (esRAGE), a splice variant, are soluble isoforms (sRAGE) that act as organ-protective decoys. However, the pathophysiologic roles of RAGE/sRAGE in acute kidney injury (AKI) remain unclear. We found that AKI was more severe, with enhanced renal tubular damage, macrophage infiltration, and fibrosis, in mice lacking both RAGE and sRAGE than in wild-type (WT) control mice. Using murine tubular epithelial cells (TECs), we demonstrated that hypoxia upregulated messenger RNA (mRNA) expression of HMGB1 and tumor necrosis factor α (TNF-α), whereas RAGE and esRAGE expressions were paradoxically decreased. Moreover, the addition of recombinant sRAGE canceled hypoxia-induced inflammation and promoted cell viability in cultured TECs. sRAGE administration prevented renal tubular damage in models of ischemia/reperfusion-induced AKI and of anti-glomerular basement membrane (anti-GBM) glomerulonephritis. These results suggest that sRAGE is a novel therapeutic option for AKI.

The Value of Serum HMGB1 and sRAGE in the Diagnosis, Efficacy Monitoring and Prognosis of Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the value of high mobility group protein B1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the diagnosis, efficacy monitoring and prognosis of newly diagnosed multiple myeloma (MM) patients.@*METHODS@#Fifty newly diagnosed MM patients before and after chemotherapy and 50 hematological outpatients from October 2018 to May 2020 were selected. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum HMGB1 and sRAGE levels of the patients. ROC was used to further analyze the efficacy of serum HMGB1 and sRAGE levels on the diagnosis of MM. At the same time, the serum levels of HMGB1 and sRAGE before and after chemotherapy were compared, and their values in the evaluation of curative effect of MM patients were analyzed. According to the mean values of serum HMGB1 and sRAGE, all the patients were divided into different groups, the clinical characteristics and survival status of the patients were compared.@*RESULTS@#Before treatment the serum HMGB1 level of the patients in MM group was higher than that in control group, while sRAGE level was lower (t=11.363,6.127, P<0.001). The AUC of serum HMGB1 and sRAGE in the MM patients was 0.955 and 0.811, respectively. After 3 courses of chemotherapy, HMGB1 level of the patients in CR group was lower than before chemotherapy, while in PD group was higher, as well as sRAGE level of the patients in PR group (P<0.05). There were significant differences in R-ISS stage, HGB, CRP, ESR, CD56, CD117, D13S319 deletion between HMGB1 high expression group and HMGB1 low expression group (χ2=3.920, 6.522, 6.65, 4.16, 3.945, 6.65, 4.16, P<0.05), while there were significant differences in ISS stage, CRP and CD56 between sRAGE low expression group (28 cases) and sRAGE high expression group (22 cases) (χ2=4.565, 4.711, 5.547, P<0.05). Kaplan-Meier survival analysis showed that the patients in HMGB1 low expression group had better survival condition, for PFS Tlow>Thigh (χ2=9.470, P<0.05), and for OS Tlow>Thigh (χ2=7.808, P<0.05); there was no difference in the survival of sRAGE high expression group and low expression group, for PFS Tlow<Thigh (χ2=1.661, P>0.05), and for OS Tlow<Thigh (χ2=2.048, P>0.05). Cox analysis showed that LDH and HMGB1 were the factors affecting the prognosis of the patients, and both of them affected PFS (HR=2.771, 95% CI: 1.002-7.662, P=0.049; HR=6.022, 95% CI: 1.689-21.470, P=0.006), while HMGB1 also affected OS (HR=4.275, 95% CI: 1.183-15.451, P=0.027).@*CONCLUSION@#The serum HMGB1 and sRAGE have certain auxiliary value for the diagnosis and curative effect monitoring of newly diagnosed MM patients, and serum HMGB1 is expected to be an auxiliary detection index for the prognosis of MM.

Advanced Glycation End-Products (AGEs) and Their Soluble Receptor (sRAGE) in Women Suffering from Systemic Lupus Erythematosus (SLE).

Systemic lupus erythematosus (SLE) is characterized by abnormal action of the immune system and a state of chronic inflammation. The disease can cause life-threatening complications. Neoepitopes arising from interdependent glycation and oxidation processes might be an element of SLE pathology. The groups included in the study were 31 female SLE patients and 26 healthy female volunteers (the control group). Blood serum samples were obtained to evaluate concentrations of advanced glycation end-products (AGEs), carboxymethyllysine (CML), carboxyethyllysine (CEL), pentosidine, and a soluble form of the receptor for advanced glycation end-products (sRAGE). Compared to a healthy control group, the SLE patients exhibited a higher concentration of AGEs and a lower concentration of sRAGE in serum. There were no statistically significant differences in serum CML, CEL, and pentosidine concentrations between the groups. Therefore, SLE patients could be at risk of intensified glycation process and activation of the proinflammatory receptor for advanced glycation end-products (RAGE), which could potentially worsen the disease course; however, it is not clear which compounds contribute to the increased concentration of AGEs in the blood. Additionally, information about the cigarette smoking and alcohol consumption of the study participants was obtained.

Elevated level of the soluble receptor for advanced glycation end-products involved in sarcopenia: an observational study.

BACKGROUND: The soluble receptor for advanced glycation end products (sRAGE) has been proposed to serve as a marker for disease severity, but its role in sarcopenia, an age-related progressive loss of muscle mass and function, remains elusive. This study examines the association between sRAGE and sarcopenia. METHODS: A total of 314 community-dwelling elderly adults who had their health examination at Tri-Service General Hospital from 2017 to 2019 underwent protein analysis with enzyme-linked immunosorbent assay. The relationship with sarcopenia and its detailed information, including components and diagnosis status, were examined using linear and logistic regressions. RESULTS: As for sarcopenia components, low muscle mass (ß = 162.8, p = 0.012) and strength (ß = 181.31, p = 0.011) were significantly correlated with sRAGE, but not low gait speed (p = 0.066). With regard to disease status, confirmed sarcopenia (ß = 436.93, p < 0.001), but not probable (p = 0.448) or severe sarcopenia (p = 0.488), was significantly correlated with sRAGE. In addition, females revealed a stronger association with sRAGE level by showing significant correlations with low muscle mass (ß = 221.72, p = 0.014) and low muscle strength (ß = 208.68, p = 0.043). CONCLUSIONS: sRAGE level showed a positive association with sarcopenia, illustrating its involvement in the evolution of sarcopenia. This association is more evident in female groups, which may be attributed to the loss of protection from estrogen in postmenopausal women. Utilizing sRAGE level as a prospective marker for sarcopenia deserves further investigation in future studies.

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

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.

Circulating Advanced Glycation End Products and Their Soluble Receptors in Relation to All-Cause and Cardiovascular Mortality: A Systematic Review and Meta-analysis of Prospective Observational Studies.

Advanced glycation end products (AGEs) are involved in the development of several age-related complications. The protective role of soluble receptors for AGEs (sRAGE) against deleterious effects of AGEs has been indicated in several studies. However, findings on the association of AGEs or sRAGE with mortality are equivocal. In this meta-analysis we aimed to present a quantitative estimation of the association between circulating AGEs or sRAGE and all-cause or cardiovascular disease (CVD) mortality. A comprehensive literature search was performed to determine relevant publications through the online databases including PubMed, Scopus, and Web of Science up to 29 November 2020. Prospective observational studies assessing the association between circulating AGEs or sRAGE and all-cause or CVD mortality were included. Seven studies with a total of 3718 participants and 733 mortality cases (345 CVD deaths) were included in the meta-analysis for assessing the association between circulating AGEs and mortality. Our results showed that higher circulating AGEs were associated with increased risk of all-cause (pooled effect measure: 1.05; 95% CI: 1.01, 1.09; P = 0.018, I2 = 77.7%) and CVD mortality (pooled effect measure: 1.08; 95% CI: 1.01, 1.14; P = 0.015, I2 = 80.2%), respectively. The association between sRAGE and mortality was assessed in 14 studies with a total of 16,335 participants and 2844 mortality cases (419 CVD deaths). Serum concentrations of sRAGE were not associated with the risk of all-cause mortality (pooled effect measure: 1.01; 95% CI: 1.00, 1.01; P = 0.205, I2 = 75.5%), whereas there was a significant link between sRAGE and the risk of CVD mortality (pooled effect measure: 1.02; 95% CI: 1.00, 1.04; P = 0.02, I2 = 78.9%). Our findings showed that a higher serum AGE concentration was associated with increased risk of all-cause and CVD mortality. In addition, higher circulating sRAGE was related to increased risk of CVD mortality. This review was registered at PROSPERO as CRD42021236559.

Correlation between soluble receptor for advanced glycation end products levels and coronary artery disease in postmenopausal nondiabetic women.

BACKGROUND: The established cardiovascular risk factors cannot explain the overall risk of coronary artery disease (CAD), especially in women. Therefore, there is a growing need for the assessment of novel biomarkers to identify women at risk. The receptor for advanced glycation end products (RAGE) and its interaction with the advanced glycation end product (AGE) ligand have been associated with atherogenesis. The soluble fraction of RAGE (sRAGE) antagonizes RAGE signaling and exerts an antiatherogenic effect. AIM: The study aim was to explore the association between plasma levels of sRAGE and CAD in nondiabetic postmenopausal women. METHODS: This case-control study included 110 nondiabetic postmenopausal women who were enrolled in two groups. Group I included 55 angiographically proven CAD subjects with > 50% stenosis in at least one of the major coronary arteries and Group II included 55 healthy control women who did not have CAD or had < 50% stenosis of the coronary arteries. Stenosis was confirmed by invasive angiography. Plasma sRAGE was determined by an enzyme-linked immunosorbent assay. RESULTS: We observed significantly lower plasma sRAGE concentrations in subjects with CAD vs healthy controls (P < 0.05). Univariate and multivariate logistic regression analysis also revealed a significant correlation between plasma sRAGE levels and CAD (P = 0.01). Multivariate odds ratios for CAD revealed that subjects with sRAGE concentrations below 225 pg/mL (lowest quartile) had a 6-fold increase in CAD prevalence independent of other risk factors. CONCLUSION: Our findings indicated that low sRAGE levels were independently associated with CAD in nondiabetic postmenopausal women. Risk assessment of CAD in postmenopausal women can be improved by including sRAGE along with other risk factors.

The use of the soluble receptor for advanced glycation-end products (sRAGE) as a potential biomarker of disease risk and adverse outcomes.

The soluble receptor for advanced glycation end-products (sRAGE) has been classically considered a sink for pro-inflammatory RAGE ligands and as such has been associated with protection from inflammatory stress and disease. An alternative, though not mutually exclusive view is that high levels of sRAGE in circulation reflect the overstimulation of cell surface RAGE which if persistent, lead to the amplification of pro-inflammatory processes and the exacerbation of pathological states. With these two scenarios in mind this review focuses on the potential role of sRAGE as a prospective biomarker of disease risk and adverse outcomes.