Lowering of dietary advanced glycation endproducts (AGE) reduces neointimal formation after arterial injury in genetically hypercholesterolemic mice

Reigh Yi Lin, Ernane D. Reis, Anthony T. Dore, Min Lu, Newsha Ghodsi, John T. Fallon, Edward A. Fisher, Helen Vlassara

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

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 1 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 (∼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 ∼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.

Original languageEnglish
Pages (from-to)303-311
Number of pages9
JournalAtherosclerosis
Volume163
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Advanced glycation endproducts
  • Hypercholesterolemia
  • Neointimal formation

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