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Am J Pathol. 2009 Oct;175(4):1722-32. doi: 10.2353/ajpath.2009.090138. Epub 2009 Sep 24.

Advanced glycation end product receptor-1 transgenic mice are resistant to inflammation, oxidative stress, and post-injury intimal hyperplasia.

Author information

1
Division of Experimental Diabetes and Aging, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.

Abstract

The high levels of oxidative stress (OS) and inflammation associated with cardiovascular disease are linked to pro-oxidants such as advanced glycation end products (AGEs). AGEs interact with multiple receptors, including receptor 1 (AGER1), which promotes AGE removal and blocks OS and inflammation, and RAGE, which enhances inflammation. In this study, we evaluated metabolic and vascular changes in AGER1 transgenic mice (AGER1-tg) subjected to an atherogenic diet and arterial wire-injury. Both baseline and postatherogenic diet serum and tissue AGEs as well as plasma 8-isoprostane levels were lower in AGER1-tg mice than in wild-type mice. The levels of injected (125)I-AGE in tissues were decreased as well in AGER1-tg mice. After ingesting a high-fat diet, AGER1-tg mice had a normal glucose tolerance and only 7% were hyperglycemic, whereas 53% of wild-type mice had stable hyperglycemia. After wire-injury, intimal lesions in AGER1-tg mice were small, whereas wild-type mice had diffuse intimal hyperplasia, a high intima/media ratio, and inflammatory cell infiltrates. In addition, AGER1 staining, prominent in AGER1-tg mice, was attenuated in 30 to 40% of wild-type cells, although all cells were strongly positive for AGEs. Thus, AGER1 overexpression in mice reduces basal levels of AGEs and OS, enhances resistance to diet-induced hyperglycemia and OS, and protects against injury-induced arterial intimal hyperplasia and inflammation, providing protection against OS and inflammation induced by AGEs and high-fat diets in vivo.

PMID:
19779136
PMCID:
PMC2751567
DOI:
10.2353/ajpath.2009.090138
[Indexed for MEDLINE]
Free PMC Article

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