title: Regional and global protective effects of tissue kallikrein gene delivery to the peri-infarct myocardium.
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.
  
  
  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.
authors.affiliation: Interuniversity Consortium, INBB, Osilo and Alghero, Italy.
authors.forename: Frank
authors.initials: F
authors.lastname: Spillmann
authors.forename: Gallia
authors.initials: G
authors.lastname: Graiani
authors.forename: Sophie
authors.initials: S
authors.lastname: Van Linthout
authors.forename: Marco
authors.initials: M
authors.lastname: Meloni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Campesi
authors.forename: Costanza
authors.initials: C
authors.lastname: Lagrasta
authors.forename: Dirk
authors.initials: D
authors.lastname: Westermann
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
authors.forename: Federico
authors.initials: F
authors.lastname: Quaini
authors.forename: Costanza
authors.initials: C
authors.lastname: Emanueli
authors.forename: Paolo
authors.initials: P
authors.lastname: Madeddu
mesh_terms: D000818:Animals; D002470:Cell Survival; D003331:Coronary Vessels / Q000254:growth & development; D003971:Diastole / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics* / Q000401:mortality / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000235:genetics / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology; D013234:Stem Cells / Q000166:cytology; D013599:Systole / Q000502:physiology; D020840:Tissue Kallikreins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020257:Ventricular Remodeling
chemical_list: D020840:Tissue Kallikreins