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West Virginia IDeA Network of Biomedical
Research Excellence |
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Robert Harris
West Virginia State UniversityResponse
of Vascular Smooth Muscle Cells to Stretch
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 Abstract: The economic and human
cost of cardiovascular disease has resulted in intense research
interest in the mechanisms which regulate vascular smooth muscle (VSM)
contraction and growth. It is now clear that mechanical forces
imposed on VSM in the vessel wall are important modulators of cell
structure and function. It is further recognized that organizational
changes in the actin cytoskeleton are essential for effective
contraction, mechanotransduction and signaling in different cell
types. However, the exact nature of cytoskeletal reorganization has
not been studied and the mechanisms regulating these changes are
largely unknown in VSM. A goal of this study is to elucidate the
acute response in cytoskeletal reorganization and associated changes
in protein regulation during mechanical stretch of smooth muscle
cells. Utilizing molecular approaches combined with confocal
microscopy we will 1) evaluate the role of actin and microtubular
components of the cytoskeleton on the cell orientation response to
stretch; 2) determine the role of the mitogen-activated protein
kinase (MAPK) signal transduction pathway in the cell orientation
and cytoskeletal organization response to stretch and; 3) the effect
of stretch-induced cytoskeletal reorganization on expression of key
signal transduction and focal adhesion proteins. The use of
pharmacologic and molecular techniques to stabilize, destabilize or
downregulate specific cytoskeletal components is expected to provide
clear answers concerning the role of specific components in
mechanotransduction and the cell orientation response. The
inhibition or downregulation of specific signaling proteins is
expected to provide information concerning pathways regulating
mechanosensing and transduction. The knowledge gained may be useful
in the development of therapeutic agents regulating
mechanotransduction mechanisms contributing to cardiovascular
pathologies. Consistent with the WV-INBRE objective, the proposal will
establish a collaborative research focus on mechanotransduction in
VSM unique within West Virginia. |
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