Lowering of dietary advanced glycation endproducts (AGE) reduces neointimal formation after arterial injury in genetically hypercholesterolemic mice
Lowering of dietary advanced glycation endproducts (AGE) reduces neointimal formation after arterial injury in genetically hypercholesterolemic mice
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DOI：
10.1016/s0021-9150(02)00008-4
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发表时间：
2002-08-01
期刊：
影响因子：
5.3
通讯作者：
Vlassara, H
中科院分区：
文献类型：
--
作者：
Lin, RY;Reis, ED;Vlassara, H
呼吸暂停仍然是冠状动脉成形术后发病率和死亡率的主要原因。损伤诱导的炎症、血栓形成、平滑肌细胞（SMC）增殖和新生内膜形成有助于再狭窄。这些事件与循环葡萄糖衍生的晚期糖基化终产物（AGE）有关，已知其可促进细胞增殖、脂质糖基化和氧化应激。本研究评估了饮食中AGE含量与遗传性高胆固醇血症小鼠动脉损伤后新生内膜形成之间的关系。将12周龄的雄性载脂蛋白E缺陷（apoE（-/-））小鼠随机分配接受高AGE饮食（HAD; AGE = 15 000 U/mg）或AGE低10倍的类似饮食（LAD; AGE = 1500 U/mg）。一周后，这些小鼠遭受股动脉损伤，并再维持4周的饮食。损伤后4周，LAD喂养小鼠的新生内膜形成显著减少。LAD组新生内膜面积、内膜/中膜比值和狭窄管腔面积（LA）均小于HAD组（P < 0.05）。这些定量差异与新生内膜病变中巨噬细胞的显著减少（类似于56%）以及LAD喂养小鼠SMC含量的明显减少相关。LAD小鼠中新生内膜形成的减少与循环AGE水平下降40%相关（P < 0.0005）。免疫组织化学还显示LAD喂养小鼠新生内膜病变中内皮、SMC和巨噬细胞中AGE沉积减少（< 1.5倍）。这些结果代表了饮食AGE和血管壁对急性损伤的反应之间因果关系的第一个体内证据，表明饮食AGE限制在预防血管成形术后再狭窄中的重要潜力。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Restenosis remains a major cause of morbidity and mortality after coronary angioplasty. Injury-induced inflammation, thrombosis, smooth muscle cell (SMC) proliferation, and neointimal formation contribute to restenosis. These events are linked to circulating glucose-derived advanced gycation endproducts (AGE), known to promote cell proliferation, lipid glycoxidation and oxidant stress. This study evaluates the association between dietary AGE content and neointimal formation after arterial injury in genetically hypercholesterolemic mice. Male, 12-week-old, apolipoprotein E-deficient (apoE(-/-)) mice were randomly assigned to receive either a high AGE diet (HAD; AGE = 15 000 U/mg), or a similar diet with ten-fold lower AGE (LAD; AGE = 1500 U/mg). These mice underwent femoral artery injury I week later, and were maintained on their diets for an additional 4 weeks. At 4 weeks after injury, significant decrease in neointimal formation was noted in LAD-fed mice. Neointimal area, intima/media ratio, and stenotic luminal area (LA) were less pronounced in the LAD group than the HAD group (P < 0.05). These quantitative differences were associated with a marked reduction (similar to 56%) of macrophages in the neointimal lesions, as well as an obvious reduction of SMC content of LAD-fed mice. The reduction of neointimal formation in the LAD mice correlated with a similar to 40% decrease in circulating AGE levels (P < 0.0005). Immunohistochemistry also showed a reduced (< 1.5-fold) deposition of AGE in the endothelia, SMC, and macrophages in neointimal lesions of LAD-fed mice. These results represent the first evidence in vivo for a causal relationship between dietary AGE and the vessel wall response to acute injury, suggesting a significant potential for dietary AGE restriction in the prevention of restenosis after angioplasty. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.