Regional and global protective effects of tissue kallikrein gene delivery to the peri-infarct myocardium.

Frank Spillmann, Gallia Graiani, Sophie Van Linthout, Marco Meloni, Ilaria Campesi, Costanza Lagrasta, Dirk Westermann, Carsten Tschöpe, Federico Quaini, Costanza Emanueli, Paolo Madeddu

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The kallikrein-kinin system participates in the maintenance of the cardiovascular phenotype. We previously demonstrated that human tissue kallikrein gene (hTK) transfer promotes the healing of ischemic limbs. The present investigation aimed to test the original hypothesis that hTK delivery to the peri-infarct myocardium would prevent post-ischemic heart failure. METHODS AND RESULTS: Myocardial infarction (MI) was induced in anesthetized mice by permanently occluding the left coronary descendant. hTK was delivered to the peri-infarct myocardium via an adenoviral vector (Ad.hTK). Controls received Ad.Null or saline. Survival rate was similar among groups. Ad.hTK increased the number of circulating endothelial progenitor cells and promoted the growth of capillaries and arterioles in the peri-infarct myocardium. In addition, Ad.hTK increased the abundance of cardiac progenitor cells (CPCs) in the peri-infarct and suppressed the apoptotic death of peri-infarct cardiomyocytes in vivo and ex vivo. As a consequence of these beneficial effects, at 5 weeks from MI, hTK-transduced hearts were protected from post-MI ventricular dilatation and showed better systolic and diastolic functions. CONCLUSIONS: Ad.hTK benefits the neovascularization and viability of peri-infarct myocardium and increases CPC abundance, thereby decreasing ventricular dysfunction. Our study significantly adds to the knowledge of the protective effects of TK gene transfer on ischemic diseases and opens new avenues for the treatment of post-MI cardiac failure.

Original languageEnglish
Pages (from-to)235-254
Number of pages20
JournalRegenerative Medicine
Volume1
Issue number2
DOIs
Publication statusPublished - Mar 2006

ASJC Scopus subject areas

  • Biomedical Engineering
  • Embryology

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    Spillmann, F., Graiani, G., Van Linthout, S., Meloni, M., Campesi, I., Lagrasta, C., Westermann, D., Tschöpe, C., Quaini, F., Emanueli, C., & Madeddu, P. (2006). Regional and global protective effects of tissue kallikrein gene delivery to the peri-infarct myocardium. Regenerative Medicine, 1(2), 235-254. https://doi.org/10.2217/17460751.1.2.235