Dietary glycotoxins promote diabetic atherosclerosis in apolipoprotein E-deficient mice
Dietary glycotoxins promote diabetic atherosclerosis in apolipoprotein E-deficient mice
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DOI：
10.1016/s0021-9150(03)00050-9
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发表时间：
2003-06-01
期刊：
影响因子：
5.3
通讯作者：
Vlassara, H
中科院分区：
文献类型：
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作者：
Lin, RY;Choudhury, RP;Vlassara, H
高血糖衍生的晚期糖基化终末产物(AGE)与糖尿病动脉粥样硬化(AS)有关，但外源性(饮食)AGE在这一严重并发症的发生中的作用尚不清楚，本研究评估了饮食相关AGE对遗传高胆固醇血症载脂蛋白E缺陷(apoE(-/-))、链脲佐菌素诱导的糖尿病小鼠AS的影响。将6-8周龄的糖尿病和非糖尿病载脂蛋白E(-/-)小鼠随机分为两组，一组为标准AIN-93G饲料(日龄12500+/-700U/mg，称为高龄饲料，H-AGE)，另一组为低4~5倍日龄水平的高龄饲料(L-AGE：2700+/-830U/mg)。糖尿病2个月后，与饲喂标准(H-AGE)饲料的糖尿病小鼠相比，L年龄组小50%的主动脉根部AS病变(0.17±0.03vs.0.31±0.05 mm(2)，P<；0.05)。糖尿病L组血清AGE低于H组(接近53%)(P<；0.00001)，与非糖尿病L组和H组相似(P<；0.05)。没有注意到与饮食有关的血糖、甘油三酯或血浆胆固醇的变化。免疫组织化学比较显示，L-AGE糖尿病组组织AGE、AGE-1、-2和RAGE表达明显抑制，炎细胞、组织因子、血管细胞黏附分子-1和单核细胞趋化蛋白-1的数量减少。这一发现支持了饮食摄入预先形成的糖氧化产物、组织结合年龄和糖尿病加速AS之间的重要联系。在该模型中，限龄饮食具有显著的抗动脉粥样硬化作用，可能为相关的临床研究提供依据。(C)2003爱思唯尔爱尔兰科学有限公司。保留所有权利。
Hyperglycemia derived advanced glycation endproducts (AGE) have been implicated in diabetic atherosclerosis (AS) but the role of exogenous (dietary) AGE in the development of this serious complication is not known, This study evaluates the influence of diet-related AGE on AS in genetically hypercholesterolemic apolipoprotein E-deficient (apoE(-/-)), streptozotocin-induced diabetic mice. Diabetic and non-diabetic apoE(-/-) mice (6-8 weeks old) were randomized into either a standard AIN-93G chow (AGE 12 500 +/- 700 U/mg, termed high-AGE diet, H-AGE), or the same chow having four to fivefold lower AGE level (L-AGE: 2700 +/- 830 U/mg) based on ELISA. After 2 months of diabetes, compared to the diabetic mice fed standard (H-AGE) diet, the AS lesions at the aortic root of the L-AGE group were > 50% smaller (0.17 +/- 0.03 vs. 0.31 +/- 0.05 mm(2), P < 0.05). Serum AGE were lower in the diabetic L-AGE than in the H-AGE mice (by similar to 53%) (P < 0.00001), as were in the non-diabetic L-AGE vs. H-AGE groups (P < 0.05). No diet-related changes were noted in plasma glucose, triglycerides, or plasma cholesterol. Inummohistochemical comparisons showed markedly suppressed tissue AGE, AGE-Receptor-1, -2 and RAGE expression, reduced numbers of inflammatory cells, tissue factor, vascular cell adhesion molecule-1 and MCP-1 in the L-AGE diabetic group. The findings are supportive of an important link between dietary intake of pre-formed glycoxidation products, tissue-incorporated AGE, and diabetes-accelerated AS. The marked anti-atherogenic effects of an AGE-restricted diet in this model may provide the basis for relevant clinical studies. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.