Advanced Glycation End Product Receptor-1 Transgenic Mice Are Resistant to Inflammation, Oxidative Stress, and Post-Injury Intimal Hyperplasia

Division of Experimental Diabetes and Aging, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
American Journal Of Pathology (Impact Factor: 4.6). 09/2009; 175(4):1722-32. DOI: 10.2353/ajpath.2009.090138
Source: PubMed

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.

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Available from: Massimo Torreggiani, Aug 21, 2015
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    • "Other data suggested that over-expression of AGE-R1 can suppress AGE-induced reactive oxygen species (ROS) generation by inhibition of epidermal growth factor (EGF) receptor signalling [103] and down regulation of P66 shc , which is a pro-oxidant gene [104] in two respective studies. Furthermore, a study in AGE-R1 transgenic mice showed that these mice have lower systemic levels of AGEs and ROS, as well as being more resistant to high-fat diet induced hyperglycaemia [105]. The anti-inflammatory role of AGE- R1 was further evidenced by a human study where both healthy adults and patients with chronic kidney disease when subjected to diet lower in AGE content may lower oxidative stress/inflammation and restore AGE-R1 levels [106]. "
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