The Role Of Egr-1 In Calcific Aortic Valve Stenosis Marjan Ghazvini
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P162. The Role of Egr-1 in Calcific Aortic Valve Stenosis Marjan Ghazvini-Boroujerdi1, Jie Xu1, Bo Jian1, Senator Hazelwood1, Navneet Narula2, Robert J. Levy1 1 The Childrens Hospital of Philadelphia, Philadelphia, Pennsylvania, United States; 2The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States OBJECTIVES: Previous studies have demonstrated that the transcription factor, Egr-1, is present in atherosclerotic plaque, but not in normal aorta. We investigated the hypothesis that Egr-1 is present in calcified heart valve cusps because of the unique presence in calcified heart valves of proteins known to be regulated by Egr-1, such as Tenascin C and TGF-Beta. METHODS: Immunohistochemistry studies with an anti-Egr-1 antibody were performed in microscopic sections from non-calcified (5 specimens) and calcified human aortic valves (10 specimens). Sheep aortic valve interstitial cell (SAVIC) cultures were used as a model system to investigate the effects of Egr-1 on the mechanistic events contributing to aortic valve calcification. RESULTS: Immunohistochemistry studies demonstrated that all calcified cusps were strongly positive for Egr-1, localized in inflammatory and interstitial cells. However, normal cusps, showed only rare intracellular Egr-1. SAVIC’s cultivated on native collagen calcified in culture, but did not upregulate Egr-1, whereas SAVIC’s grown on denatured collagen did not calcify, but upregulated Egr-1. Furthermore, SAVIC’s overexpressing either full length Egr-1 or partially deleted Egr-1, amino acids 174-270 deleted (Delta Egr-1), were created using plasmid vectors with zeosin selection. SAVIC’s overexpressing Egr-1 demonstrated significantly less calcification in culture than did either the Delta-Egr-1 cells or controls. CONCLUSIONS: Egr-1 is present in calcific aortic stenosis cusps and may regulate anti- calcification activity.