Targeting kinin B-1 receptor for therapeutic neovascularization

Targeting kinin B-1 receptor for therapeutic neovascularization

Author Emanueli, C. Google Scholar
Salis, M. B. Google Scholar
Stacca, T. Google Scholar
Pintus, G. Google Scholar
Kirchmair, R. Google Scholar
Isner, J. M. Google Scholar
Pinna, A. Google Scholar
Gaspa, L. Google Scholar
Regoli, D. Google Scholar
Cayla, C. Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
Bader, Michael Autor UNIFESP Google Scholar
Madeddu, P. Google Scholar
Institution INBB Natl Lab
Univ Sassari
St Elizabeths Med Ctr
Univ Ferrara
Max Delbruck Ctr Mol Med
Universidade Federal de São Paulo (UNIFESP)
Abstract 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.
Keywords receptors, bradykinin
angiogenesis
ischemia
muscle, skeletal
endothelium
Language English
Date 2002-01-22
Published in Circulation. Philadelphia: Lippincott Williams & Wilkins, v. 105, n. 3, p. 360-366, 2002.
ISSN 0009-7322 (Sherpa/Romeo, impact factor)
Publisher Lippincott Williams & Wilkins
Extent 360-366
Origin http://dx.doi.org/10.1161/hc0302.102142
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000173466100021
URI http://repositorio.unifesp.br/handle/11600/26733

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