Targeting kinin B-1 receptor for therapeutic neovascularization

• Autor(a) principal: Emanueli, C.
• Data de Publicação: 2002
• Outros Autores: Salis, M. B., Stacca, T., Pintus, G., Kirchmair, R., Isner, J. M., Pinna, A., Gaspa, L., Regoli, D., Cayla, C., Pesquero, João Bosco [UNIFESP], Bader, Michael [UNIFESP], Madeddu, P.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1161/hc0302.102142; http://repositorio.unifesp.br/handle/11600/26733
• topic: receptors, bradykinin; angiogenesis; ischemia; muscle, skeletal; endothelium

Background-Kinins are modulators of cardiovascular function. After ischemic injury, enhanced kinin generation may contribute in processes responsible for tissue healing.Methods and Results-Using pharmacological and genetic approaches, we investigated the role of kinin B-1 receptor in reparative angiogenesis in a murine model of limb ischemia. the effect of B-1 pharmacological manipulation on human endothelial cell proliferation and apoptosis was also studied in vitro, Abrogation of B-1 signaling dramatically inhibited the native angiogenic response to ischemia, severely compromising blood perfusion recovery. Outcome was especially impaired in B-1 knockouts that showed a very high incidence of limb necrosis, eventually leading to spontaneous auto-amputation. Conversely, local delivery of a long-acting B-1 receptor agonist enhanced collateral vascular growth in ischemic skeletal muscle, accelerated the rate of perfusion recovery, and improved limb salvage. in vitro, B-1 activation stimulated endothelial cell proliferation and survival, whereas B-1 antagonism induced apoptosis,Conclusions-Our results indicate that the B-1 plays an essential role in the host defense response to ischemic injury. B-1 signaling potentiation might be envisaged as a utilitarian target for the treatment of ischemic vascular disease.