Adenovirus-mediated human tissue kallikrein gene delivery inhibits neointima formation induced by interruption of blood flow in mice

Costanza Emanueli, Maria Bonaria Salis, Julie Chao, Lee Chao, Jun Agata, Kuei Fu Lin, Antonella Munaò, Stefania Straino, Alessandra Minasi, Maurizio C. Capogrossi, Paolo Madeddu

Research output: Contribution to journalArticle

Abstract

Tissue kallikrein cleaves kininogen to produce vasoactive kinin peptides. Binding of kinins to bradykinin B2 receptors on vascular endothelial cells stimulates the release of nitric oxide and prostacyclin, thus activating the cGMP and cAMP pathways. In this study, we evaluated the effects of adenovirus-mediated human tissue kailikrein gene (Ad.CMV-cHK) delivery in a mouse model of arterial remodeling induced by permanent alteration in shear stress conditions. Mice underwent ligature of the left common carotid artery and were injected intravenously with saline or 1.8X109 plaque-forming units of Ad.CMV-cHK or control virus (Ad. CMV-LacZ). Fourteen days after surgery, morphometric analysis revealed that Ad. CMV-cHK reduced neointima formation by 52% (P2 receptor gene compared with wild-type control mice (J129Sv mice). In contrast' the effect of Ad. CMV-cHK was amplified (P2 receptor compared with wild-type control mice (c57/BI6 mice). Thus, the inhibitory effect of recombinant kallikrein on structural alterations caused by the interruption of blood flow appears to be mediated by the B2 receptor. These results provide new insight into the role of the tissue kallikrein-kinin system in vascular remodeling and suggest the application of HK gene therapy to treat restenosis and atherosclerosis.

Original languageEnglish
Pages (from-to)1459-1466
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume20
Issue number6
Publication statusPublished - Jun 2000

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Keywords

  • Bradykinin B receptors
  • Gene delivery
  • Human tissue kallikrein
  • Mice, transgenic and knockout
  • Neointima formation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Emanueli, C., Salis, M. B., Chao, J., Chao, L., Agata, J., Lin, K. F., Munaò, A., Straino, S., Minasi, A., Capogrossi, M. C., & Madeddu, P. (2000). Adenovirus-mediated human tissue kallikrein gene delivery inhibits neointima formation induced by interruption of blood flow in mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 20(6), 1459-1466.