Neovascularization includes a number of biological events which are associated with endothelial cell modulation and proliferation, and which are prominent features of biological and pathological processes such as wound healing, neoplasia, inflammation, diabetic retinopathy, and embryonic development. The major question addressed here is how endothelial cells, once stimulated to divide, become organized into a network of capillaries which is then remodelled into a complex microvasculature having a pattern characteristic of individual tissues. The hypothesis to be tested is that one regulatory component of vascular differentiation and patterning derives from the interaction between endothelial cells and the surrounding extracellular matrix. That is, secretion or degredation of extracellular matrix molecules by endothelial cells or surrounding cells can mediate the structural differentiation of blood vessels or their component cells and can help determine the pattern of vessels within a tissue. Using two models of angiogenesis, the neovascularized rabbit cornea and the developing chick chorioallantoic membrane, the specific aims are to: (1) continue to characterize the precise composition and arrangement of matrix molecules in the basal laminae and adjacent tissue surrounding developing vessels, and determine the sequence in which specific matrix molecules are added to the basal laminae, (2) determine whether the structure or patterning of new vessels is altered by interfering with matrix structure or deposition, and (3) characterize the changes in surface carbohydrates induced in endothelial cells during angiogenesis. These studies will employ light and electron microscopy, histochemistry, immunohistochemistry and autoradiography. In a separate but complementary in vitro study, the possible involvement of the endothelial cell cytoskeleton in mediating the cellular effects of extracellular matrix molecules and selected angiogenic factors will be investigated. This study will employ cultured capillary endothelial cells and ultrastructural study of cell whole mounts.
|Dethlefsen, S M; Butterfield, C E; Ausprunk, D H (1986) Structural changes induced in capillary endothelial cells by growth factors: altered distribution of cytoskeletal elements and organelles in cells spreading in the presence of tumor conditioned medium and hypothalamus derived growth factor. Tissue Cell 18:827-37|