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This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 295/2/E323    most recent 00024.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tikellis, C. Articles by Forbes, J. M. Search for Related Content PubMed PubMed Citation Articles by Tikellis, C. Articles by Forbes, J. M.

Cardiac inflammation associated with a Western diet is mediated via activation of RAGE by AGEs

¹Baker Heart Research Institute, Melbourne, Victoria, Australia; and ²Department of Medicine, University of Heidelberg, Heidelberg, Germany

Submitted 14 January 2008 ; accepted in final form 8 May 2008

A diet high in fat induces cardiac hypertrophy, inflammation, and oxidative stress. Although such actions have largely been ascribed to fat deposition, the accumulation of advanced glycation end products (AGEs) and subsequent activation of the receptor for AGEs (RAGE) may also represent important mediators of cardiac injury following exposure to a Western diet. In this study, male C57BL6J and RAGE knockout mice were placed on either a standard diet (7% fat) or a Western "fast-food" diet (21% fat). Animals receiving a high-fat diet were further randomized to receive the AGE inhibitor alagebrium chloride (1 mg·kg^–1·day^–1) and followed for 16 wk. A Western diet was associated with cardiac hypertrophy, inflammation, mitochondrial-dependent superoxide production, and cardiac AGE accumulation in wild-type mice. Although RAGE-KO mice fed a Western diet also became obese and accumulated intramyocardial lipid, cardiomyocyte hypertrophy, inflammation, and oxidative stress were attenuated compared with wild-type mice. Similarly, mice of both strains receiving alagebrium chloride had reduced levels of inflammation and oxidative stress, in association with a reduction in cardiac AGEs and RAGE. This study suggests that AGEs represent important mediators of cardiac injury associated with a Western fast-food diet. These data point to the potential utility of AGE-reducing strategies in the prevention and management of cardiac disease.

advanced glycation end products; receptor for advanced glycation end products; inflammation; cardiac disease