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Abstract:
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Mitral valve diseases and disorders affect tens of thousands of Americans each year, but
understanding of the disease processes has yet to be fully developed. The behavior and
characteristics of valve cells and tissue are highly dependent on their surrounding
environment, including neighboring cells, extracellular matrix composition and 3D
structure, mechanical forces, and signaling molecules both in the tissue and the
circulation. In order to study native valve behavior and responses, an ex vivo bioreactor
system was developed to culture whole mitral valves. The organ culture system simulated
a physiologically relevant mechanical environment and provided nutrients and gas
exchange. Valves cultured in this dynamic system retained more native cell and tissue
characteristics than valves cultured in a static environment. To utilize this novel tool, a
study was conducted to determine the effects of Angiotensin II on mitral valves, alone
and in combination with the statin drug, Simvastatin.Angiotensin II was found to alter the
native valve composition. Simvastatin inhibited some of these alterations, but accentuated
others and also affected separate valve characteristics. In conclusion, an organ culture
system for mitral valves has been designed, characterized, validated, and effectively put
to use in a novel study. |
