Despite recent advances in treatment, cardiovascular diseases continue to be leading causes of mortality in the United States. Major congenital malformations of heart valves and the great arteries also present significant challenges, since children who require valve or arterial replacement typically outgrow the replacement structures. The substitute heart valves and blood vessels currently available have significant limitations; presently, autologous tissue replacements appear to provide the best combination of safety, performance and longevity. To improve upon existing heart valve and vessel replacement options, the collaborators (Drs. Mayer, Vacanti, and Langer) have tissue-engineered single pulmonary valve leaflets from autologous vascular cells and shown that these structures function for months in a growing lamb. This dramatic result was achieved without an in-depth knowledge of the cellular and molecular properties of native valves. The investigators hypothesize that cardiac valves have unique properties that are important for structure and function. Furthermore, understanding these unique properties at a biochemical and molecular level will be required to fully optimize and exploit the tissue-engineering of vascular replacement structures. Towards this end, the investigators propose to analyze and define the biochemical and functional properties of endothelial and stromal cells of normal human and ovine pulmonary valves. Second, the investigators will analyze tissue-engineered structures produced by Drs. Mayer, Vacanti, and Langer for expression of biochemical markers present in normal valves. Third, the investigators will identify regulated genes by a suppression subtractive hybridization approach. These studies will allow the investigators to define differential expression of both known and novel genes in the endothelial and stromal cells of normal valves and in tissue-engineered vascular structures. The same experimental approach will be applied to large and small arteries. The ability to study vascular cells in vitro and then in vivo provides a unique opportunity to analyze vascular growth and remodeling at a molecular level.
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