title: Tissue inhibitor of metalloproteinase-2 gene delivery ameliorates postinfarction cardiac remodeling.
abstract: OBJECTIVE
  Adenoviral-mediated (AdV-T2) overexpression of TIMP-2 would blunt ventricular remodeling and improve survival in a murine model of chronic ischemic injury.
  
  
  METHODS
  Male mice (n = 124) aged 10-14 weeks underwent either (1) left coronary artery ligation to induce myocardial infarction (MI group, n = 36), (2) myocardial injection of 6 × 10¹⁰ viral particles of AdV-T2 immediately post-MI (MI + T2 group, n = 30), (3) myocardial injection of 6 × 10¹⁰ viral particles of a control adenovirus (MI + Ct, n = 38), or 4) received no intervention (controls, n = 20). On post-MI day 7, surviving mice (n = 79) underwent echocardiographic, immunohistochemical, and biochemical analysis.
  
  
  RESULTS
  In infarcted animals, the MI + T2 group demonstrated improved survival (p < 0.02), better preservation of developed pressure and ventricular diameter (p < 0.04), and the lowest expression and activity of MMP-2 and MMP-9 (p < 0.04) compared with MI and MI + Ct groups. All infarcted hearts displayed significantly increased inflammatory cell infiltration (p < 0.04 vs. control, MI, or MI + T2), with infiltration highest in the MI + Ct group and lowest in the MI + T2 group (p < 0.04).
  
  
  CONCLUSIONS
  Adenoviral mediated myocardial delivery of the TIMP-2 gene improves post-MI survival and limits adverse remodeling in a murine model of MI.
authors.affiliation: Cardiovascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. ramanirn@upmc.edu
authors.forename: Ravi
authors.initials: R
authors.lastname: Ramani
authors.forename: Kathleen
authors.initials: K
authors.lastname: Nilles
authors.forename: Gregory
authors.initials: G
authors.lastname: Gibson
authors.forename: Benjamin
authors.initials: B
authors.lastname: Burkhead
authors.forename: Michael
authors.initials: M
authors.lastname: Mathier
authors.forename: Dennis
authors.initials: D
authors.lastname: McNamara
authors.forename: Charles F
authors.initials: CF
authors.lastname: McTiernan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D004106:Dilatation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007150:Immunohistochemistry; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology* / Q000628:therapy*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D016019:Survival Analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics* / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D020782:Matrix Metalloproteinases