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

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

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

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