The proposed work is an extension of our current experiments, whereby we produce stenosis of the aorta of the rat using a U-shaped metal clip; the aorta is then perfused with glutaraldehyde, and either studied by electron microscopy or further perfused with AgNO3 to determine the topography and type of endothelial damage. We have also identified a significant improvement of the silver method, whereby the metallic silver deposit in the interendothelial junctions becomes much finer and more precise. Combining these two approaches, we plan to: (1) Study the nature and topography of the endothelial damage that is induced (in the stenotic area) by increased shear stress; (2) Study quantitatively the endothelium that re-grows into the stenotic area, and becomes adapted to increased shear stress (morphometric study of cell thickness, number and length of junctions, number and type of intracellular fibrils, number and size of """"""""microtendons"""""""" or anchoring fibrils, etc.); (3) Study the long-range (6 months) adaptation of the endothelium in the stenotic area; (4) Produce aortic stenosis by a different method, i.e., by using a silver clip that pinches one side of the aorta, and compare the results obtained with the present method.
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