| Matrix metalloproteinase inhibition attenuates atrial remodeling and vulnerability to atrial fibrillation in a canine model of heart failure. | |
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MedLine Citation:
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PMID: 18995182 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Atrial structural remodeling occurs in evolving heart failure (HF) and is an important substrate for the development of atrial fibrillation (AF). The matrix metalloproteinases (MMPs) play a role in extracellular remodeling, and recent studies have demonstrated increased atrial MMP activity in HF. Whether increased MMP activity directly contributes to atrial remodeling and AF in the setting of HF remains unclear. The current study examined the effects of MMP inhibition on atrial structural remodeling and AF vulnerability during HF progression. METHODS AND RESULTS: Three groups of dogs (n = 5 each)--control normal dogs (controls) and 10 dogs subjected to simultaneous atrioventricular pacing (SAVP) for 2 weeks to induce HF and randomly assigned to treatment with placebo (SAVP-placebo) or a MMP inhibitor PGE-7113313, a MMP-1-sparing MMP inhibitor, 6 mg/kg orally twice daily (SAVP-MMPi)--were studied. SAVP-MMPi dogs had less AF inducibility (percent of burst attempts leading to AF episodes: 1.7 +/- 2.9 seconds vs. 23+/-19 seconds, mean +/- SD, P < .05) and maintenance (AF duration: 253 [105 to 326] vs. 1932 [1296 to 2724] seconds, median [25th-75th quartile], P < .05) than SAVP-placebo dogs. The SAVP-MMPi dogs had significantly smaller increases in atrial myocyte cross sectional area, collagen area fraction, and MMP-9 activity relative to controls than SAVP-placebo. There were, however, no significant differences in the changes in chamber dimension and function in the left atrium. CONCLUSIONS: This unique finding of an attenuation of the vulnerability to AF in conjunction with reduced myocyte hypertrophy and fibrosis after MMP inhibition suggests that heightened MMP activity in the atria contributes to atrial structural remodeling and AF promotion during evolving HF. |
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Authors:
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Gordon W Moe; Gabriel Laurent; Liia Doumanovskaia; Andrea Konig; Xudong Hu; Paul Dorian |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2008-08-22 |
Journal Detail:
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Title: Journal of cardiac failure Volume: 14 ISSN: 1532-8414 ISO Abbreviation: J. Card. Fail. Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-11-10 Completed Date: 2009-06-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9442138 Medline TA: J Card Fail Country: United States |
Other Details:
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Languages: eng Pagination: 768-76 Citation Subset: IM |
Affiliation:
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Division of Cardiology, St. Michael's Hospital, Toronto, Ontario, Canada. moegord@attglobal.net |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atrial Fibrillation / drug therapy, enzymology*, etiology Disease Models, Animal Disease Susceptibility / enzymology, etiology, physiopathology Dogs Heart Failure / complications, drug therapy, enzymology* Matrix Metalloproteinases / antagonists & inhibitors*, metabolism Protease Inhibitors / pharmacology, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Protease Inhibitors; EC 3.4.24.-/Matrix Metalloproteinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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