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.

Targeting kinin B-1 receptor for therapeutic neovascularization / Emanueli, C; Salis, Mb; Stacca, T; Pintus, Gianfranco; Kirchmair, R; Isner, Jm; Pinna, A; Gaspa, L; Regoli, D; Cayla, C; Pesquero, Jb; Bader, M; Madeddu, P.. - In: CIRCULATION. - ISSN 0009-7322. - 105:3(2002), pp. 360-366. [10.1161/hc0302.102142]

Targeting kinin B-1 receptor for therapeutic neovascularization

PINTUS, Gianfranco;
2002

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.
Targeting kinin B-1 receptor for therapeutic neovascularization / Emanueli, C; Salis, Mb; Stacca, T; Pintus, Gianfranco; Kirchmair, R; Isner, Jm; Pinna, A; Gaspa, L; Regoli, D; Cayla, C; Pesquero, Jb; Bader, M; Madeddu, P.. - In: CIRCULATION. - ISSN 0009-7322. - 105:3(2002), pp. 360-366. [10.1161/hc0302.102142]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/47801
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