Open AccessTissue Inhibitor of Metalloproteinase‐2 Gene Delivery Ameliorates Postinfarction Cardiac Remodeling
Author(s) -
Ramani Ravi,
Nilles Kathleen,
Gibson Gregory,
Burkhead Benjamin,
Mathier Michael,
McNamara Dennis,
McTiernan Charles F.
Publication year - 2011
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/j.1752-8062.2010.00252.x
Subject(s) - medicine , myocardial infarction , ventricular remodeling , cardiology , ligation , tissue inhibitor of metalloproteinase , gene delivery , sham surgery , genetic enhancement , matrix metalloproteinase , pathology , gene , biology , biochemistry , alternative medicine
Hypothesis: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 × 10 10 viral particles of AdV‐T2 immediately post‐MI (MI + T2 group, n = 30), (3) myocardial injection of 6 × 10 10 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. Clin Trans Sci 2011; Volume 4: 24–31