| Tissue inhibitor of metalloproteinase-2 gene delivery ameliorates postinfarction cardiac remodeling. | |
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MedLine Citation:
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PMID: 21348952 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Ravi Ramani; Kathleen Nilles; Gregory Gibson; Benjamin Burkhead; Michael Mathier; Dennis McNamara; Charles F McTiernan |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical and translational science Volume: 4 ISSN: 1752-8062 ISO Abbreviation: Clin Transl Sci Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-25 Completed Date: 2011-06-06 Revised Date: 2012-02-02 |
Medline Journal Info:
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Nlm Unique ID: 101474067 Medline TA: Clin Transl Sci Country: United States |
Other Details:
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Languages: eng Pagination: 24-31 Citation Subset: IM |
Copyright Information:
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© 2011 Wiley Periodicals, Inc. |
Affiliation:
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Cardiovascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. ramanirn@upmc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cardiomegaly / etiology, pathology, physiopathology Collagen / metabolism Dilatation Gene Therapy* Gene Transfer Techniques* 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:
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U01 HL066949-01/HL/NHLBI NIH HHS; U01HL66949/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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127497-59-0/Tissue Inhibitor of Metalloproteinase-2; 9007-34-5/Collagen; EC 3.4.24.-/Matrix Metalloproteinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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