Dietary glycotoxins promote diabetic atherosclerosis in apolipoprotein E-deficient mice

Reigh Yi Lin, Robin P. Choudhury, Weijing Cai, Min Lu, John T. Fallon, Edward A. Fisher, Helen Vlassara

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

Abstract

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 mm2, P<0.05). Serum AGE were lower in the diabetic L-AGE than in the H-AGE mice (by ∼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. Immunohistochemical 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.

Original languageEnglish
Pages (from-to)213-220
Number of pages8
JournalAtherosclerosis
Volume168
Issue number2
DOIs
StatePublished - 1 Jun 2003

Keywords

  • Atheroma
  • Diet
  • Glycation
  • Vascular disease

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