Tissue Inhibitor of Metalloproteinase-2 Gene Delivery Ameliorates Postinfarction Cardiac Remodeling

Overview

Journal Clin Transl Sci

Specialties Biomedical Engineering
General Medicine

Date 2011 Feb 26

PMID 21348952

Citations 10

Authors

Ravi Ramani

Kathleen Nilles

Gregory Gibson

Benjamin Burkhead

Michael Mathier

Dennis McNamara

Charles F McTiernan

Affiliations

Soon will be listed here.

Abstract

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 × 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.

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