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Early plasma soluble receptor for advanced glycation end-product levels are associated with bronchiolitis obliterans syndrome.

ABSTRACT: Early epithelial injury after lung transplantation may contribute to development of bronchiolitis obliterans syndrome (BOS). We evaluated the relationship between early postoperative soluble receptor for advanced glycation end-product (sRAGE) levels, a marker of type I alveolar cell injury and BOS. We performed a cohort study of 106 lung transplant recipients between 2002 and 2006 at the University of Pennsylvania with follow-up through 2010. Plasma sRAGE was measured 6 and 24 h after transplantation. Cox proportional hazards models were used to evaluate the association between sRAGE and time to BOS, defined according to ISHLT guidelines. Sixty (57%) subjects developed BOS. The average time to BOS was 3.4 years. sRAGE levels measured at 6 h (HR per SD of sRAGE: 1.69, 95% CI: 1.11, 2.57, p = 0.02) and 24 h (HR per SD of sRAGE: 1.74, 95% CI: 1.14, 2.65, p = 0.01) were associated with an increased hazard of BOS. Multivariable Cox regression indicated this relationship was independent of potential confounders. Elevated plasma sRAGE levels measured in the immediate postoperative period are associated with the development of BOS. Early epithelial injury after transplantation may contribute to the development of fibrosis in BOS.

SUBMITTER: Shah RJ

PROVIDER: S-EPMC3582806 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Early plasma soluble receptor for advanced glycation end-product levels are associated with bronchiolitis obliterans syndrome.

Shah R J RJ Bellamy S L SL Lee J C JC Cantu E E Diamond J M JM Mangalmurti N N Kawut S M SM Ware L B LB Christie J D JD

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20130117 3

Early epithelial injury after lung transplantation may contribute to development of bronchiolitis obliterans syndrome (BOS). We evaluated the relationship between early postoperative soluble receptor for advanced glycation end-product (sRAGE) levels, a marker of type I alveolar cell injury and BOS. We performed a cohort study of 106 lung transplant recipients between 2002 and 2006 at the University of Pennsylvania with follow-up through 2010. Plasma sRAGE was measured 6 and 24 h after transplant ...[more]

PMID: 23331756

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Project description:Abstract Background. RAGE, a multi-ligand type 1 transmembrane glycoprotein belonging to the immunoglobulin superfamily, transduces biological signals associated with chronic cellular stress related with inflammatory responses, tissue damage, chronic and degenerative diseases (1). sRAGE is a variant of RAGE derived from cell surface cleavage mechanisms that could potentially act as endogenous inhibitors of RAGE activity (2). RAGE gene is highly polymorphic, with polymorphisms that could be responsible for disease development, like -374T/A (rs1800624) and -429T/C (rs1800625) polymorphisms. These are located in the promoter region and have marked effect on transcriptional activity. However, there have been conflicting findings between the potential association of RAGE polymorphisms and the development of diseases. In this work, we evaluated -374T/A (rs1800624) and -429T/C (rs1800625) polymorphisms and measured serum sRAGE levels in Mexican population with MS. Methods. A group of healthy men without any component of the MS (n=80), and a group of men with the MS (n=80) according to the harmonized criteria for the MS were included in this study. Blood genomic DNA was isolated and genotyped by RT-PCR for the -374T/A and -429T/C polymorphisms of RAGE gene. sRAGE in serum was measured with an ELISA kit. Results. The studied population complied with the Hardy-Weinberg equilibrium (p=0.58 for -374T/A, and p=0.79 for -429T/C). Differences were observed in all the components of the MS between the two groups (MS vs. healthy subjects, p<0.000). However, there were no differences in the population according to their genotype for the -374T/A (p=0.57) and -429T/C (p=0.59) polymorphisms. There was no difference in glucose (p=0.22), triglycerides (p=0.99), and cHDL (p=0.88) levels, or waist circumference (p=0.84) according to the genotype for the -374T/A polymorphism. The same was observed for the -429T/C polymorphism (glucose p=0.57, triglycerides p=0.69, cHDL p=0.77, waist circumference p=0.99). No association of MS with the -374T/A nor 429T/C polymorphism was found. There were no differences between groups in circulating sRAGE levels (p=0.132). Conclusion. According to our results, the -374T/A and -429T/C polymorphisms of RAGE gene are not associated with the MS in Mexican population, and have no influence on serum sRAGE levels. Some other factors could be playing a role for the high prevalence of the MS, such as eating habits. Gender should be taken into consideration, for our study was performed in men exclusively. References. (1) Serveaux-Dancer M et al., Dis Markers. 2019 Feb 4;2019:2067353. (2) Schmidt AM. Vascul Pharmacol. 2015 Sep;72:1-8.

Project description:BackgroundAdvanced glycation end products (AGEs) promote adverse health effects and may contribute to the multi-system functional decline observed in aging. Diet is a major source of AGEs, and foods high in protein may increase circulating AGE concentrations. However, epidemiological evidence that high-protein diets increase AGEs is lacking.ObjectivesWe examined whether dietary protein intake was associated with serum concentrations of the major AGE carboxymethyl-lysine (CML) and the soluble receptor for AGEs (sRAGE) in 2439 participants from the Health, Aging, and Body Composition study (mean age, 73.6 ± 2.9 y; 52% female; 37% black).MethodsCML and sRAGE were measured by ELISA, and the CML/sRAGE ratio was calculated. Protein intake was estimated using an interviewer-administered FFQ and categorized based on current recommendations for older adults: <0.8 g/kg/d (n = 1077), 0.8 to <1.2 g/kg/d (n = 922), and ≥1.2 g/kg/d (n = 440). Associations between protein intake and AGE-RAGE biomarkers were examined using linear regression models adjusted for demographics, height, lifestyle behaviors, prevalent disease, cognitive function, inflammation, and other dietary factors.ResultsCML concentrations were higher in individuals with higher total protein intake (adjusted least squares mean ± SE: <0.8 g/kg/d, 829 ± 17 ng/ml; 0.8 to <1.2 g/kg/d, 860 ± 15 ng/ml; ≥1.2 g/kg/d, 919 ± 23 ng/ml; P for trend = 0.001), as were sRAGE concentrations (<0.8 g/kg/d, 1412 ± 34 pg/ml; 0.8 to <1.2 g/kg/d, 1479 ± 31 pg/ml; ≥1.2 g/kg/d, 1574 ± 47 pg/ml; P for trend < 0.0001). Every 0.1 g/kg/d increment in total protein intake was associated with a 13.3 ± 3.0 ng/ml increment in CML and a 22.1 ± 6.0 pg/ml increment in sRAGE (P < 0.0001 for both). Higher CML and sRAGE concentrations were also associated with higher intakes of both animal and vegetable protein (all P values ≤ 0.01). There were no significant associations with the CML/sRAGE ratio.ConclusionsHigher dietary protein intake was associated with higher CML and sRAGE concentrations in older adults; however, the CML/sRAGE ratio remained similar across groups.

Dataset Information

Early plasma soluble receptor for advanced glycation end-product levels are associated with bronchiolitis obliterans syndrome.

Publications

Early plasma soluble receptor for advanced glycation end-product levels are associated with bronchiolitis obliterans syndrome.

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