Targeting kinin B1 receptor for therapeutic neovascularization

Costanza Emanueli, Maria Bonaria Salis, Tiziana Stacca, Gianfranco Pintus, Rudolf Kirchmair, Jeffrey M. Isner, Alessandra Pinna, Leonardo Gaspa, Domenico Regoli, Cecile Cayla, Joao B. Pesquero, Michael Bader, Paolo Madeddu

Research output: Contribution to journalArticle

104 Citations (Scopus)

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 B1 receptor in reparative angiogenesis in a murine model of limb ischemia. The effect of B1 pharmacological manipulation on human endothelial cell proliferation and apoptosis was also studied in vitro. Abrogation of B1 signaling dramatically inhibited the native angiogenic response to ischemia, severely compromising blood perfusion recovery. Outcome was especially impaired in B1 knockouts that showed a very high incidence of limb necrosis, eventually leading to spontaneous auto-amputation. Conversely, local delivery of a long-acting B1 receptor agonist enhanced collateral vascular growth in ischemic skeletal muscle, accelerated the rate of perfusion recovery, and improved limb salvage. In vitro, B1 activation stimulated endothelial cell proliferation and survival, whereas B1 antagonism induced apoptosis. Conclusions - Our results indicate that the B1 plays an essential role in the host defense response to ischemic injury. B1 signaling potentiation might be envisaged as a utilitarian target for the treatment of ischemic vascular disease.

Original languageEnglish
Pages (from-to)360-366
Number of pages7
JournalCirculation
Volume105
Issue number3
DOIs
Publication statusPublished - Jan 22 2002

Fingerprint

Kinins
Ischemia
Extremities
Endothelial Cells
Perfusion
Cell Proliferation
Pharmacology
Apoptosis
Limb Salvage
Wounds and Injuries
Vascular Diseases
Amputation
Blood Vessels
Cell Survival
Skeletal Muscle
Necrosis
Therapeutics
Incidence
Growth
In Vitro Techniques

Keywords

  • Angiogenesis
  • Endothelium
  • Ischemia
  • Muscle, skeletal
  • Receptors, bradykinin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Emanueli, C., Salis, M. B., Stacca, T., Pintus, G., Kirchmair, R., Isner, J. M., ... Madeddu, P. (2002). Targeting kinin B1 receptor for therapeutic neovascularization. Circulation, 105(3), 360-366. https://doi.org/10.1161/hc0302.102142

Targeting kinin B1 receptor for therapeutic neovascularization. / Emanueli, Costanza; Salis, Maria Bonaria; Stacca, Tiziana; Pintus, Gianfranco; Kirchmair, Rudolf; Isner, Jeffrey M.; Pinna, Alessandra; Gaspa, Leonardo; Regoli, Domenico; Cayla, Cecile; Pesquero, Joao B.; Bader, Michael; Madeddu, Paolo.

In: Circulation, Vol. 105, No. 3, 22.01.2002, p. 360-366.

Research output: Contribution to journalArticle

Emanueli, C, Salis, MB, Stacca, T, Pintus, G, Kirchmair, R, Isner, JM, Pinna, A, Gaspa, L, Regoli, D, Cayla, C, Pesquero, JB, Bader, M & Madeddu, P 2002, 'Targeting kinin B1 receptor for therapeutic neovascularization', Circulation, vol. 105, no. 3, pp. 360-366. https://doi.org/10.1161/hc0302.102142
Emanueli C, Salis MB, Stacca T, Pintus G, Kirchmair R, Isner JM et al. Targeting kinin B1 receptor for therapeutic neovascularization. Circulation. 2002 Jan 22;105(3):360-366. https://doi.org/10.1161/hc0302.102142
Emanueli, Costanza ; Salis, Maria Bonaria ; Stacca, Tiziana ; Pintus, Gianfranco ; Kirchmair, Rudolf ; Isner, Jeffrey M. ; Pinna, Alessandra ; Gaspa, Leonardo ; Regoli, Domenico ; Cayla, Cecile ; Pesquero, Joao B. ; Bader, Michael ; Madeddu, Paolo. / Targeting kinin B1 receptor for therapeutic neovascularization. In: Circulation. 2002 ; Vol. 105, No. 3. pp. 360-366.
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