Cited by 381Advanced Glycation End Products researchAldose Reductase and TaurineChronic Kidney Disease and Diabetes

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The RAGE Axis: A Fundamental Mechanism Signaling Danger to the Vulnerable Vasculature

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Yan, Shi Fang, Ramasamy, Ravichandran, Schmidt, Ann Marie·2010·Circulation Research

DOI 10.1161/circresaha.109.212217PMC PMC2862596

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Abstract

The immunoglobulin superfamily molecule RAGE (receptor for advanced glycation end product) transduces the effects of multiple ligands, including AGEs (advanced glycation end products), advanced oxidation protein products, S100/calgranulins, high-mobility group box-1, amyloid-beta peptide, and beta-sheet fibrils. In diabetes, hyperglycemia likely stimulates the initial burst of production of ligands that interact with RAGE and activate signaling mechanisms. Consequently, increased generation of proinflammatory and prothrombotic molecules and reactive oxygen species trigger further cycles of oxidative stress via RAGE, thus setting the stage for augmented damage to diabetic tissues in the face of further insults. Many of the ligand families of RAGE have been identified in atherosclerotic plaques and in the infarcted heart. Together with increased expression of RAGE in diabetic settings, we propose that release and accumulation of RAGE ligands contribute to exaggerated cellular damage. Stopping the vicious cycle of AGE-RAGE and RAGE axis signaling in the vulnerable heart and great vessels may be essential in controlling and preventing the consequences of diabetes.

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Authors: Yan, S. F., Ramasamy, R., & Schmidt, A. M.
Affiliations: Columbia University (US)
ORCID: Yan, Shi Fang
Ramasamy, Ravichandran
Schmidt, Ann Marie
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2010-03-19
Volume: 106
Issue: 5
Pages: 842-853
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/circresaha.109.212217
PMC: PMC2862596
OpenAlex: W2118046722
Cited by: 381
References: 100
Citations by year: 2026: 11 · 2025: 18 · 2024: 10 · 2023: 17 · 2022: 22 · 2021: 22 · 2020: 21 · 2019: 20 · 2018: 23 · 2017: 25 · 2016: 21 · 2015: 26 · 2014: 34 · 2013: 34 · 2012: 34
FWCI: 3.64
Type: journal article
Language: en
Update notices: correction (2010-04-30)
Open access: bronze
doi.org
Locations: Circulation Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (P01AG026467)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Keywords: receptor for advanced glycation end products, RAGE, advanced glycation end products, advanced oxidation protein products, S100/calgranulins, high mobility group box 1, amyloid-beta, β-sheet fibrils, diabetes mellitus, hyperglycemia, oxidative stress, inflammation, thrombosis, atherosclerosis, diabetic cardiomyopathy
MeSH terms: Receptor for Advanced Glycation End Products, Animals, Blood Vessels, Cardiovascular Diseases, Diabetes Mellitus, Humans, Immunity, Innate, Ligands, Polymorphism, Genetic, Protein Processing, Post-Translational, Receptors, Immunologic, Signal Transduction, Diabetes Complications, Adaptive Immunity

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The RAGE Axis: A Fundamental Mechanism Signaling Danger to the Vulnerable Vasculature

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