| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| Estudo da função do gene Delta4 na regulação da angiogénese | 71.03 MB | Adobe PDF |
Authors
Abstract(s)
O sistema vascular é um dos mais importantes nos mamíferos, sendo o primeiro a
tornar-se funcional durante o desenvolvimento embrionário. A sua formação requer uma coordenação complexa de diversos mecanismos genéticos e celulares. O estudo destes mecanismos é de grande importância para o desenvolvimento de novas terapias que pretendam inibir ou promover a formação de novos vasos sanguíneos (neoangiogénese).
A via de sinalização Notch está envolvida na diferenciação de uma grande variedade de
tipos celulares. Esta tese descreve um trabalho de investigação com o objectivo de caracterizar a função de um novo ligando da via Notch (Delta4), no desenvolvimento vascular em mamíferos.
Para isso recorreu-se à análise de uma linha de ratinhos com inactivação de um ou dos dois
alelos do gene Delta4. A caracterização fenotípica destes mutantes permitiu descobrir que o gene é essencial para a diferenciação e desenvolvimento dos vasos arteriais e que uma diminuição da sinalização Notch induzida por este ligando aumenta a sensibilidade das células endoteliais a estímulos angiogénicos.
No seu conjunto os resultados mostram que o gene Delta4 é fundamental para o
desenvolvimento normal dos vasos sanguíneos, podendo ter também um papel importante na
neoangiogénese do adulto, pelo que constitui um alvo terapêutico a explorar.
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.
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.
Description
Tese de Doutoramento em Ciência e Tecnologia Animal
Keywords
Delta4 Notch Angiogénese Arteriogénese Desenvolvimento Vascular Angiogenesis Arteriogenesis Vascular Development
Pedagogical Context
Citation
Publisher
Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária