Document Detail


Tissue inhibitor of metalloproteinase-2 gene delivery ameliorates postinfarction cardiac remodeling.
MedLine Citation:
PMID:  21348952     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ravi Ramani; Kathleen Nilles; Gregory Gibson; Benjamin Burkhead; Michael Mathier; Dennis McNamara; Charles F McTiernan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and translational science     Volume:  4     ISSN:  1752-8062     ISO Abbreviation:  Clin Transl Sci     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-25     Completed Date:  2011-06-06     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  101474067     Medline TA:  Clin Transl Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  24-31     Citation Subset:  IM    
Copyright Information:
© 2011 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Cardiomegaly / etiology,  pathology,  physiopathology
Collagen / metabolism
Dilatation
Gene Transfer Techniques*
Genetic Therapy*
Immunohistochemistry
Male
Matrix Metalloproteinases / metabolism
Mice
Mice, Inbred C57BL
Myocardial Infarction / complications,  physiopathology*,  therapy*
Myocardium / enzymology,  pathology
Survival Analysis
Tissue Inhibitor of Metalloproteinase-2 / genetics*,  therapeutic use*
Ventricular Remodeling / physiology*
Grant Support
ID/Acronym/Agency:
U01 HL066949-01/HL/NHLBI NIH HHS; U01HL66949/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
127497-59-0/Tissue Inhibitor of Metalloproteinase-2; 9007-34-5/Collagen; EC 3.4.24.-/Matrix Metalloproteinases
Comments/Corrections

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