Abstract
Aging is considered to be the major risk factor for cardiovascular diseases, including atherosclerosis. In aging, accumulation of advanced glycation endproducts (AGEs) and their interaction with receptor for advanced glycation end product (RAGE) may contribute to age-related endothelial dysfunction. Soluble RAGE (sRAGE) blocks the interaction of AGEs with their receptor, and hence acts as an antagonist for RAGE. The effect of intraperitoneal sRAGE treatment (500 μg/300g animal) on improving age-related endothelial dysfunction was examined in aged Fisher 344 rats. Endothelium dependent relaxation (EDR) was measured in aortic rings from young rats (4 months), aged rats (26 months), and aged rats treated with 3 or 10 days of sRAGE. Rings were mounted in conventional organ baths and pre-contracted with phenylephrine (PE). EDR to acetylcholine (Ach; 10−8–10−4M) was measured as % relaxation to PE±SEM. EDR was significantly impaired in aged rats compared with young rats. 10 day sRAGE treatment resulted in a significant improvement of EDR in aged rats to levels similar to those observed in young rats. These data indicate that RAGE antagonism may be a viable therapy for treating age-related vascular dysfunction. Supported by NIH HL60901
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