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podendo ter também um papel importante na neoangiogénese do adulto, pelo que constitui um alvo terapêutico a explorar. Study of the Delta4 function in the regulation of angiogenesis Abstract The vascular system is one of the most important in mammals and the first to become functional during embryonic development. Its formation requires the complex coordination of several genetic and cellular mechanisms. Understanding these mechanisms is highly important for the development of new therapies devised to inhibit or promote the formation of new blood vessels (neoangiogenesis). The Notch signalling pathway allows the differentiation of a wide variety of cell types. This thesis describes the research work aimed at characterizing the role of a novel Notch ligand (Delta4) in the mammalian vascular development. In order to approach this, a mouse line with the inactivation of either one or both alleles of the Delta4 gene was analyzed. The phenotypic characterization of these mutants allowed us to discover that this gene is essential for the differentiation and development of the arteries, and that a decrease in the ligand induced Notch signalling increases endothelial cell sensibility to the angiogenic stimulus. Taken together, these results show that the Delta4 gene is essential for the normal blood vessel development and that it might also have an important role in the adult neoangiogenesis constituting a novel therapeutic target to be explored. 9 Estrutura e função de…

sistema fechado. As idas e vindas de um pensamento vivo e desafiador pouco a pouco tenderam a dar lugar a uma visão de mundo esclerosada. Enquanto durou a União Soviética, o marxismo foi ensinado como ideologia oficial e a economia planificada pelo comitê central apresentada como se fosse bom exemplo de uma economia sem mercado. Isso durou até que a União Soviética se desintegrasse e os outros sistemas socialistas passassem a incorporar formas de produção mercantil. Ainda hoje se ouve o…