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N-Epsilon-(carboxymethyl)lysine is unable to induce endothelial dysfunction but is able to attenuate Ages-induced endothelium damage in human umbilical vein endothelial cells.

PMID 23700790


N-Epsilon-carboxymethyllysine (CML), one of the main compounds in advanced glycation end products (AGEs), has been thought to be a high bioaffinity ligand of the receptor for AGEs (RAGE), and is involved in the pathogenesis in endothelial dysfunction in diabetic vascular complications. However, some researchers believed that CML was unable to bind to RAGE and could not induce endothelium damage. In our present experiment, the role of CML in inducing endothelial dysfunction, preventing AGEs-induced damage and binding to RAGE was explored in human umbilical vein endothelial cells (HUVECs). The treatment with CML could not induce the endothelial dysfunction by itself, including upregulation on transforming growth factor-betai (TGF-beta1), intercellular adhesion molecule-1 (ICAM-1) and RAGE proteins expressions, apoptosis and cell viability in HUVECs. However, pretreatment with CML could attenuate AGEs-induced endothelial dysfunction. Fluorescence polarization assay showed that CML had a bioaffinity to RAGE. The IC50 of CML binding to RAGE (10 ng and 100 ng) were 7.133 x 10-8M and 1.563 x 10-6M, respectively. Our findings indicate that CML has no cytotoxic injury to endothelium but has a bioaffinity for the binding to RAGE.

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