Targeting kinin B-1 receptor for therapeutic neovascularization

Show simple item record Emanueli, C. 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. 2016-01-24T12:33:13Z 2016-01-24T12:33:13Z 2002-01-22
dc.identifier.citation Circulation. Philadelphia: Lippincott Williams & Wilkins, v. 105, n. 3, p. 360-366, 2002.
dc.identifier.issn 0009-7322
dc.description.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. en
dc.format.extent 360-366
dc.language.iso eng
dc.publisher Lippincott Williams & Wilkins
dc.relation.ispartof Circulation
dc.rights Acesso aberto
dc.subject receptors, bradykinin en
dc.subject angiogenesis en
dc.subject ischemia en
dc.subject muscle, skeletal en
dc.subject endothelium en
dc.title Targeting kinin B-1 receptor for therapeutic neovascularization en
dc.type Artigo
dc.contributor.institution INBB Natl Lab
dc.contributor.institution Univ Sassari
dc.contributor.institution St Elizabeths Med Ctr
dc.contributor.institution Univ Ferrara
dc.contributor.institution Max Delbruck Ctr Mol Med
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation INBB Natl Lab, Cardiovasc Med & Gene Therapy Sect, I-07033 Osilo, Sassari, Italy
dc.description.affiliation Univ Sassari, I-07100 Sassari, Italy
dc.description.affiliation St Elizabeths Med Ctr, Boston, MA USA
dc.description.affiliation Univ Ferrara, I-44100 Ferrara, Italy
dc.description.affiliation Max Delbruck Ctr Mol Med, Berlin, Germany
dc.description.affiliation Universidade Federal de São Paulo, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, São Paulo, Brazil
dc.identifier.doi 10.1161/hc0302.102142
dc.description.source Web of Science
dc.identifier.wos WOS:000173466100021


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