Grossin Nicolas, Auger Florent, Niquet-Leridon Céline, Durieux Nicolas, Montaigne David, Schmidt Ann Marie, Susen Sophie, Jacolot Philippe, Beuscart Jean-Baptiste, Tessier Frédéric J, Boulanger Eric
Inserm U995/Team "Glycation: from inflammation to aging", Lille School of Medicine, Lille University, Lille, France.
Mol Nutr Food Res. 2015 May;59(5):927-38. doi: 10.1002/mnfr.201400643. Epub 2015 Mar 20.
Advanced glycation end-products (AGEs) are endogenously produced and are present in food. N(ε)-carboxymethyllysine (CML) is an endothelial activator via the receptor for AGEs (RAGEs) and is a major dietary AGE. This work investigated the effects of a CML-enriched diet and RAGE involvement in aortic aging in mice.
After 9 months of a control diet or CML-enriched diets (50, 100, or 200 μg(CML)/g of food), endothelium-dependent relaxation, RAGE, vascular cell adhesion molecule-1, and sirtuin-1 expression, pulse wave velocity and elastin disruption were measured in aortas of wild-type or RAGE(-/-) male C57BL/6 mice. Compared to the control diet, endothelium-dependent relaxation was reduced in the wild-type mice fed the CML-enriched diet (200 μg(CML)/g) (66.8 ± 12.26 vs. 94.3 ± 2.6%, p < 0.01). RAGE and vascular cell adhesion molecule-1 (p < 0.05) expression were increased in the aortic wall. RAGE(-/-) mice were protected against CML-enriched diet-induced endothelial dysfunction. Compared to control diet, the CML-enriched diet (200 μg(CML)/g) increased the aortic pulse wave velocity (86.6 ± 41.1 vs. 251.4 ± 41.1 cm/s, p < 0.05) in wild-type animals. Elastin disruption was found to a greater extent in the CML-fed mice (p < 0.05). RAGE(-/-) mice fed the CML-enriched diet were protected from aortic stiffening.
Chronic CML ingestion induced endothelial dysfunction, arterial stiffness and aging in a RAGE-dependent manner.
晚期糖基化终产物（AGEs）在体内生成并存在于食物中。N（ε）-羧甲基赖氨酸（CML）是一种通过晚期糖基化终产物受体（RAGEs）发挥作用的内皮激活剂，是饮食中主要的AGEs。本研究探讨了富含CML的饮食及RAGE在小鼠主动脉衰老中的作用。
对野生型或RAGE基因敲除（RAGE(-/-)）的雄性C57BL/6小鼠喂食对照饮食或富含CML的饮食（50、100或200μg（CML）/g食物）9个月后，检测其主动脉的内皮依赖性舒张功能、RAGE、血管细胞黏附分子-1和沉默调节蛋白-1的表达、脉搏波速度以及弹性蛋白破坏情况。与对照饮食相比，喂食富含CML饮食（200μg（CML）/g）的野生型小鼠内皮依赖性舒张功能降低（66.8±12.26%对94.3±2.6%，p<0.01）。主动脉壁中RAGE和血管细胞黏附分子-1的表达增加（p<0.05）。RAGE(-/-)小鼠可免受富含CML饮食诱导的内皮功能障碍影响。与对照饮食相比，富含CML的饮食（200μg（CML）/g）使野生型动物的主动脉脉搏波速度增加（86.6±41.1对251.4±41.1cm/s，p<0.05）。在喂食CML的小鼠中发现弹性蛋白破坏程度更大（p<0.05）。喂食富含CML饮食的RAGE(-/-)小鼠可免受主动脉僵硬影响。
长期摄入CML以RAGE依赖的方式诱导内皮功能障碍、动脉僵硬和衰老。
