Studies on the mechanism of angiogenesis as induced by placenta and fetal membranes

Ongay-Larios, Laura Maria (1983) Studies on the mechanism of angiogenesis as induced by placenta and fetal membranes. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Angiogenesis is the capacity of cells or tissues to elicit the growth and development of new blood vessels. Microvascular proliferation is essential in many biological and pathological processes, such as regeneration, wound healing, development of the embryo, infliltration, tumour growth and progression and a variety of disease states. Neovascularization involves complex interactions between tissue, cells and regulatory factors. There is accumulating evidence that angiogenesis is the consequence of the release of soluble mediators that may act either directly on endothelial cells or indirectly by activating mononuclear cells, which in turn generate the vascular reaction. In this study the angiogenic activity of placenta and fetal membranes was analysed and compared with tumour induced angiogenesis. In vivo and in vitro experiments were performed. The vascular response was studied both macroscopically and by histological examinations. Placental and fetal membrane, both human and rabbit in origin, were angiogenic when implanted on the CAM. Strong reactions were induced by placenta and amnion, while chorion and yolk sac were only weakly angiogenic. Boiled tissues were ineffective. Lyophilised extracts from these tissues also induced angiogenesis in this system. The angiogenic reaction was induced by chromatographic factions with different molecular weights, suggesting that the active factor may be present in different molecular forms. Neovascularization was always preceded and accompanied by a mononuclear cell infiltrate. The host origin of these cells was demonstrated by an immunohistological analysis and supported by EM observations. Activated mononuclear cells also induced angiogenesis when tested on the CAM. During angiogenesis there was migration of endothelial cells with subsequent mitosis. Observations at the microscopic and ultramicroscopic level show that capillary proliferation is not a consequence of tissue damage. Cartilage, a potent inhibitor of tumour induced angiogenesis was unable to inhibit angiogenesis induced by placenta tissue. Positive angiogenic extracts stimulated in vitro proliferation of capillary, but not aortic, endothelial cells. Proliferation of capillary endothelial cells was also stimulated by co-culturing with human mononuclear cells, and an additional response was obtained when capillary endothelial cells were cultured in the presence of both monocytes and angiogenic factors. The angiogenic factors were also chemotactic for human mononuclear cells. These results imply that angiogenic factors from placenta and fetal membranes have both a direct and an indirect effect on capillary endothelial cells, the latter being mediated via host mononuclear cells, and that the angiogenic response is regulated, at least in part, by a synergism between angigogenic factors and host mononuclear cells.

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