| Discordant activation of gene promoters for matrix metalloproteinases and tissue inhibitors of the metalloproteinases following myocardial infarction. | |
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MedLine Citation:
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PMID: 20863528 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Left ventricular (LV) remodeling following myocardial infarction (MI) is associated with increased levels of specific matrix metalloproteinases (MMPs) and relative reduction of endogenous tissue inhibitors of the MMPs (TIMPs). However, transcriptional mechanisms for the disparate post-MI MMP/TIMP expression remain unknown. Using murine constructs designed to report gene promoter activation, this study tested the hypothesis that distinctly different temporal profiles of MMP-2, MMP-9, and TIMP-1 transcription occurs post-MI. METHODS/RESULTS: Transcriptional activity (β-galactosidase (β-gal) reporter constructs) of MMP-2 (n = 49), MMP-9 (n = 62), or TIMP-1 (n = 40) was assayed at 1 h (acute), and 1-28 d after MI (coronary ligation) in transgenic reporter mice. At 7 d post-MI, the area of promoter activation normalized to LV area was increased from acute values for MMP-2 (63.4 ± 5.8 versus 1.1% ± 1.0%, P < 0.05) and MMP-9 (53.1 ± 6.1 versus 1.3% ± 0.9%, P < 0.05). While TIMP-1 promoter activation at 7 d post-MI increased from acute values (3.6 ± 1.3 versus 0.3% ± 0.5%, P < 0.05), this increase was smaller than that for MMP-2 or MMP-9 (both P < 0.05). MMP-2 promoter activation peaked in the MI region at 7 d post-MI and MMP-9 promoter activation was highest in the border region at 7 and 14 d post-MI. TIMP-1 promoter activation peaked within the MI region at 7 d post-MI and within the remote region at 14 d post-MI. CONCLUSIONS: These findings provided direct in vivo evidence that discordant changes in temporal and spatial patterns of MMP/TIMP transcription occurs with MI. Restoration of TIMP-1 promoter activation may represent a molecular therapeutic target to attenuate/prevent adverse post-MI LV remodeling. |
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Authors:
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Rupak Mukherjee; Jonathan M Snipes; Stuart M Saunders; Juozas A Zavadzkas; Francis G Spinale |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-07-02 |
Journal Detail:
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Title: The Journal of surgical research Volume: 172 ISSN: 1095-8673 ISO Abbreviation: J. Surg. Res. Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2011-12-14 Completed Date: 2012-02-14 Revised Date: 2013-02-20 |
Medline Journal Info:
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Nlm Unique ID: 0376340 Medline TA: J Surg Res Country: United States |
Other Details:
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Languages: eng Pagination: 59-67 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA. mukherr@musc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Coronary Vessels / physiopathology Disease Models, Animal Female Ligation Male Matrix Metalloproteinase 2 / genetics, metabolism* Matrix Metalloproteinase 9 / genetics, metabolism* Mice Mice, Transgenic Myocardial Infarction / metabolism*, pathology, physiopathology Myocardium / metabolism, pathology Promoter Regions, Genetic / genetics, physiology* Tissue Inhibitor of Metalloproteinase-1 / genetics, metabolism* Ventricular Remodeling beta-Galactosidase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL-45024/HL/NHLBI NIH HHS; HL-66029/HL/NHLBI NIH HHS; HL-97012/HL/NHLBI NIH HHS; M01 RR001070-290350/RR/NCRR NIH HHS; P01 HL048788-150006/HL/NHLBI NIH HHS; P01-HL48788/HL/NHLBI NIH HHS; R01 HL059165-08/HL/NHLBI NIH HHS; R01 HL066029-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Tissue Inhibitor of Metalloproteinase-1; EC 3.2.1.23/beta-Galactosidase; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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