Modulation of Soluble Receptor for Advanced Glycation End Products Isoforms and Advanced Glycation End Products in Long-Living Individuals

Scavello, Francesco; Tedesco, Calogero C.; Castiglione, Stefania; Maciąg, Anna; Sangalli, Elena; Veglia, Fabrizio; Spinetti, Gaia; Puca, Annibale Alessandro; Raucci, Angela

doi:10.2217/bmm-2020-0856

Cited by 8 publications

(10 citation statements)

References 52 publications

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“…We previously showed that circulating levels of cRAGE, and not esRAGE, decline with aging in healthy subjects and LLIs [ 31 , 32 ]. Table 3 shows the Spearman correlations of AGEs, the different isoforms of sRAGE and their ratios with age in CTR and type 2 diabetes groups.…”

Section: Resultsmentioning

confidence: 99%

“…Specifically, total human sRAGE included the detection of both cRAGE and esRAGE variants (DY1145, Human RAGE DuoSet ELISA, R&D Systems Inc., MN, USA) and esRAGE concentration was evaluated by an ELISA assay with an antibody raised against the exclusive C-terminal amino acids (332–347) sequence (K1009-1, B-bridge International, CA, USA). cRAGE was determined by subtracting esRAGE from sRAGE as already described [ 29 , 31 , 32 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Recently, the ratio of AGEs/sRAGE has been proposed as a more effective biomarker of organ damage than AGEs or sRAGE variants separately [ 31 , 45 , 46 ]. Moreover, a different predictive ability of esRAGE and cRAGE as markers of CV risk factors have been evidenced lately [ 29 , 31 , 32 ]. For instance, we have published that in a healthy population and long living individuals (LLIs), cRAGE negatively relates with aging while esRAGE is a more appropriate biomarker of obesity and longevity [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, a different predictive ability of esRAGE and cRAGE as markers of CV risk factors have been evidenced lately [ 29 , 31 , 32 ]. For instance, we have published that in a healthy population and long living individuals (LLIs), cRAGE negatively relates with aging while esRAGE is a more appropriate biomarker of obesity and longevity [ 31 , 32 ]. Hence, new aspects should be taken in consideration in order to define the prognostic value of AGEs/sRAGE isoforms axis in human pathologies.…”

Section: Introductionmentioning

confidence: 99%

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Circulating levels of AGEs and soluble RAGE isoforms are associated with all-cause mortality and development of cardiovascular complications in type 2 diabetes: a retrospective cohort study

Sabbatinelli

Castiglione

Macrì

et al. 2022

Cardiovasc Diabetol

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Background Advanced glycation end-products (AGEs) and their interaction with the receptor for advanced glycation end-products (RAGE) play a pivotal role in the development and progression of type 2 diabetes. In this retrospective cohort study, we explored the association of circulating levels of soluble RAGE (sRAGE) isoforms, i.e., endogenous secretory esRAGE and cleaved cRAGE, AGEs and their respective ratios with 15-year all-cause mortality in type 2 diabetes. Methods Baseline AGEs and sRAGE isoforms concentration were measured by ELISA in 362 patients with type 2 diabetes and in 125 age- and gender-matched healthy control subjects (CTR). Independent predictors of mortality were determined using Cox proportional-hazards models and used to build and validate a nomogram for all-cause mortality prediction in type 2 diabetes. Results AGEs, total sRAGE, cRAGE and the AGEs/sRAGE and AGEs/esRAGE ratios were significantly increased in patients with type 2 diabetes compared to CTR (p < 0.001). In CTR subjects, but not in type 2 diabetes patients, a significant negative correlation between cRAGE and age was confirmed (p = 0.003), whereas the AGEs/sRAGE (p = 0.032) and AGEs/cRAGE (p = 0.006) ratios were positively associated with age. At an average follow-up of 15 years (4,982 person-years), 130 deaths were observed. The increase in the AGEs/cRAGE ratio was accompanied by a higher risk of all-cause mortality in patients with type 2 diabetes (HR per each SD increment = 1.30, 95% CI 1.15–1.47; p < 0.001). Moreover, sRAGE was associated with the development of major adverse cardiovascular events (MACE) in type 2 diabetes patients without previous MACE (OR for each SD increase: 1.48, 95% CI 1.11–1.89). A nomogram based on age, sex, HbA1c, systolic blood pressure, and the AGEs/cRAGE ratio was built to predict 5-, 10- and 15-year survival in type 2 diabetes. Patients were categorized into quartiles of the monogram scores and Kaplan-Meier survival curves confirmed the prognostic accuracy of the model (log-rank p = 6.5 × 10− 13). Conclusions The ratio between AGEs and the cRAGE isoform is predictive of 15-year survival in patients with type 2 diabetes. Our data support the assessment of circulating AGEs and soluble RAGE isoforms in patients with type 2 diabetes as predictors of MACE and all-cause mortality.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Circulating levels of AGEs and soluble RAGE isoforms are associated with all-cause mortality and development of cardiovascular complications in type 2 diabetes: a retrospective cohort study

Sabbatinelli

Castiglione

Macrì

et al. 2022

Cardiovasc Diabetol

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Role and Therapeutic Potential of RAGE Signaling in Neurodegeneration

Kinscherf

Pehar

2022

CDT

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Activation of the receptor for advanced glycation end products (RAGE) has been shown to play an active role in the development of multiple neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis. Although originally identified as a receptor for advanced glycation end products, RAGE is a pattern recognition receptor able to bind multiple ligands. The final outcome of RAGE signaling is defined in a context and cell type specific manner and can exert both neurotoxic and neuroprotective functions. Contributing to the complexity of the RAGE signaling network, different RAGE isoforms with distinctive signaling capabilities have been described. Moreover, multiple RAGE ligands bind other receptors and RAGE antagonism can significantly affect their signaling. Here, we discuss the outcome of cell-type specific RAGE signaling in neurodegenerative pathologies. In addition, we will review the different approaches that have been developed to target RAGE signaling and their therapeutic potential. A clear understanding of the outcome of RAGE signaling in a cell type- and disease-specific manner would contribute to advance the development of new therapies targeting RAGE. The ability to counteract RAGE neurotoxic signaling while preserving its neuroprotective effects would be critical for the success of novel therapies targeting RAGE signaling.

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Oleic Acid Status Positively Correlates with the Soluble Receptor for Advanced Glycation End-Products (sRAGE) in Healthy Adults Who Are Homozygous for G Allele of RAGE G82S Polymorphism

Deo

Dhillon

Thomas

et al. 2023

Cells

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Background: The soluble form of receptor for advanced glycation end products (sRAGE) have been implicated in the prevention of numerous pathologic states, and highlights as an attractive therapeutic target. Because diets rich in monounsaturated fatty acids (MUFA) reduce postprandial oxidative stress and inflammation that is related to better health during aging, we investigated the association between red blood cell (RBC) fatty acids with circulatory AGE biomarkers and further stratified this correlation based on GG and GA + AA genotype. Methods: A total of 172 healthy participants (median age = 53.74 ± 0.61 years) were recruited for the study. RBC fatty acid was analysed using gas chromatography and sRAGE was measured using a commercial ELISA kit. Results: The result showed a non-significant correlation between total MUFA with sRAGE however oleic acid (C18:1) exhibited a positive correlation (r = 0.178, p = 0.01) that remained statistically significant (β = 0.178, p = 0.02) after a stepwise multivariate regression analysis after adjusting for age, BMI and gender. In a univariate analysis, a positive significant correlation between C18:1 and sRAGE in GG genotype (r = 0.169, p = 0.02) and a non-significant correlation with GA + AA genotype (r = 0.192, p = 0.21) was evident. When C18:1 was stratified, a significant difference was observed for oleic acid and G82S polymorphism: low C18:1/GA + AA versus high C18:1/GG (p = 0.015) and high C18:1/GA + AA versus high C18:1/GG (p = 0.02). Conclusion: Our study suggests that increased levels of C18:1 may be a potential therapeutic approach in increasing sRAGE in those with GG genotype and play a role in modulating AGE metabolism.

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Modulation of Soluble Receptor for Advanced Glycation End Products Isoforms and Advanced Glycation End Products in Long-Living Individuals

Cited by 8 publications

References 52 publications

Circulating levels of AGEs and soluble RAGE isoforms are associated with all-cause mortality and development of cardiovascular complications in type 2 diabetes: a retrospective cohort study

Circulating levels of AGEs and soluble RAGE isoforms are associated with all-cause mortality and development of cardiovascular complications in type 2 diabetes: a retrospective cohort study

Role and Therapeutic Potential of RAGE Signaling in Neurodegeneration

Oleic Acid Status Positively Correlates with the Soluble Receptor for Advanced Glycation End-Products (sRAGE) in Healthy Adults Who Are Homozygous for G Allele of RAGE G82S Polymorphism

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