Fundamental details of the formation of capillaries in neovascularizing adult tissues or in embryos remain unknown yet more knowledge seems vital to the full comprehension of the pathogenesis of diseases such as diabetes, rheumatoid arthritis and neoplasia in which neovascularization plays a significant role. To learn more about certain of these potentially vital details which may well be involved in control of capillary growth, the interaction between growing capillaries and the extracellular matrices in which they develop will be examined intensively. The major focus of the investigation is the participation of glycosaminoglycans (GAGs) in capillary development. Developing capillaries will be studied in the adult rabbit cornea after implantation of an angiogenic extract and in the chick embryo chorioallantoic membrane (CAM), using a combination of electron microscopic, autoradiographic and biochemical methods. The distribution and synthesis of specific GAGs in the perivascular extracellular matrix will be measured during various stages of capillary growth, remodeling and regression and related to the structural development of the vessel walls. Cells responsible for synthesizing the various GAGs will be identified. The relationship between the GAG composition of the matrix, endothelial and smooth muscle cell proliferation and differentiation and structural development of the vessel walls will be investigated using drugs which alter GAG synthesis, degrade specific GAGs or inhibit cell proliferation. Histochemical methods will be used to study the distribution of hyaluronic acid in the earliest stages of vessel growth. The level and substrate specificity of endogenous hyaluronidase activity in the vessel walls will be measured to determine whether enzymatic degradation contributes to altering the balance between sulfated and nonsulfated GAGs during vessel development. The immunocytochemical distribution of fibronectin at various stages of capillary growth will be mapped and the effect on vessel growth of abolition of its biologicl activity will be examined. The development of the carbohydrate composition of the endothelial and smooth muscle cell surfaces will be investigated using lectins as cytochemical markers, and compared to the timing of cytoplasmic differentiation. Finally, in embryonic vessels the role of ectoderm and endoderm in the development of capillaries will be examined using organ culture methods.
| 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 |
