Avaliação da angiogênese, inflamação e crescimento tumoral em camundongos com deleção gênica dos receptores para o PAF (PAFR-KO)

• Ano de defesa: 2006
• Autor(a) principal: Monica Alves Neves Diniz Ferreira
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Fisiologia e Farmacologia; Neovascularização; Fator de necrose de tumor; Fator de avaliação de plaquetas
• Link de acesso: http://hdl.handle.net/1843/MCSC-78AS97

The endogenous lipid, platelet activating factor (PAF), is usually considered a pro-angiogenic mediator due to its exogenous in vitroand in vivo effects and to studies with PAF receptor (PAFR) antagonists in vivo. In this study, mice with gene inactivation of the receptor for PAF (PAFR-KO) well used to analyze a range of activities exhibited by this mediator. Two experimental designs were used: the sponge implantation and the growth of solid tumors (Ehrlich and colon) to assess neovascularization, inflammation, cytokine production. Angiogenesis as determined by morphometric analysis and hemoglobin content was significantly higher in the implants and colon tumor of knock out (KO) mice compared with the wild type (WT). VEGF content in the tumors was also, higher in these animals. The levels of TNF-alpha were increased in Ehrlich tumor in KO mice relative to the WT group. Neutrophils and macrophages accumulation, as determined by myeloperoxidase (MPO) and Nacetylglucosaminidase (NAG) were decreased in all proliferatingtissues in KO animals, supporting the pro-inflammatory effects of endogenous PAF. The levels of the pro-inflammatory chemokines didnot follow the same pattern. The growth of colon tumor was not different between the KO and WT mice. However, Ehrlich tumor was six fold bigger in PAFR-KO mice than in WT animals. We have shown that inflammation and angiogenesis in PAFR-KO mice are not necessarily causal events and propose that PAF may be an important endogenous inhibitor of new blood vessels formation and Ehrlich tumor development.