The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature.
The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature.
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DOI：
10.1161/circresaha.109.212217
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发表时间：
2010-03-19
影响因子：
20.1
通讯作者：
Schmidt AM
中科院分区：
文献类型：
--
作者：
Yan SF;Ramasamy R;Schmidt AM
The immunoglobulin superfamily molecule RAGE transduces the effects of multiple ligands, including advanced glycation endproducts (AGEs), advanced oxidation protein products (AOPPs), S100/calgranulins, high mobility group box-1, amyloid-β peptide and β-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 pro-inflammatory and pro-thrombotic 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.
