Document Detail

Differential expression of matrix metalloproteinases and tissue inhibitors and extracellular matrix remodeling in aortic regurgitant hearts.
MedLine Citation:
PMID:  19129699     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Myocardial fibrosis in experimental aortic regurgitation (AR) features abnormal fibronectin with normal collagen content, but the relevant degradative processes have not been assessed. METHODS: To elucidate these degradative processes, mRNA (Northern) and protein levels (Western) of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), as well as MMP activity (zymography), were measured in cardiac fibroblasts (CF) from New Zealand white rabbits with experimental AR paired with normals (NL). Collagen and fibronectin were quantified by immunohistochemical staining. RESULTS: In AR CF versus NL CF, MMP-2 and -14 mRNA and protein were increased (both p < 0.005), while TIMPs 1-3 were slightly decreased (p < 0.05-0.005; TIMP-4 undetectable). Gelatinase activity in AR CF was 1.7 times that in NL CF (p < 0.005); fibronectinase activity was unaffected. The Jun N-terminal kinase (JNK) inhibitor SP600125 suppressed MMP-2 protein (0.4-fold, p < 0.05) and mRNA (0.7-fold, p < 0.005) in AR CF; MMP-2 levels in NL CF were unaffected. AR MMP-9 mRNA, protein and activity were low and indistinguishable from NL. In left ventricular tissue, fibronectin was increased 1.9-fold (AR vs. NL, p < 0.05). Total AR collagen was indistinguishable from NL, but the collagen III to collagen I isoform ratio decreased (0.4-fold, p < 0.05). CONCLUSIONS: Collagen is relatively deficient in AR fibrosis, due at least in part to upregulated MMPs and downregulated TIMPs; fibronectinase is unaltered. JNK-dependent regulation may stimulate both MMP-2 and fibronectin expression in AR, providing a potential therapeutic target.
Sharada L Truter; Daniel F Catanzaro; Phyllis G Supino; Anuj Gupta; John Carter; Edmund M Herrold; Themy F Dumlao; Jeffrey S Borer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-08
Journal Detail:
Title:  Cardiology     Volume:  113     ISSN:  1421-9751     ISO Abbreviation:  Cardiology     Publication Date:  2009  
Date Detail:
Created Date:  2009-05-29     Completed Date:  2009-08-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1266406     Medline TA:  Cardiology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  161-8     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 S. Karger AG, Basel.
The Division of Cardiovascular Medicine and The Howard Gilman Institute for Heart Valve Disease, State University of New York Downstate Medical Center, 47 East 88th Street, New York, NY 10128, USA.
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MeSH Terms
Aortic Valve Insufficiency / metabolism,  pathology,  physiopathology*
Cells, Cultured
Collagen Type I / metabolism
Collagen Type III / metabolism
Extracellular Matrix Proteins / metabolism
Fibrinogen / metabolism
Gene Expression / physiology
Matrix Metalloproteinase 14 / genetics,  metabolism
Matrix Metalloproteinase 2 / genetics,  metabolism
Matrix Metalloproteinase 9 / genetics,  metabolism
Matrix Metalloproteinases / genetics*,  metabolism*
Myocytes, Cardiac / cytology,  physiology*
Signal Transduction / physiology
Tissue Inhibitor of Metalloproteinase-1 / genetics,  metabolism
Tissue Inhibitor of Metalloproteinase-2 / genetics,  metabolism
Tissue Inhibitor of Metalloproteinase-3 / genetics,  metabolism
Tissue Inhibitor of Metalloproteinases / genetics*,  metabolism*
Reg. No./Substance:
0/Collagen Type I; 0/Collagen Type III; 0/Extracellular Matrix Proteins; 0/Tissue Inhibitor of Metalloproteinase-1; 0/Tissue Inhibitor of Metalloproteinase-3; 0/Tissue Inhibitor of Metalloproteinases; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; 9001-32-5/Fibrinogen; EC 3.4.24.-/Matrix Metalloproteinases; EC Metalloproteinase 2; EC Metalloproteinase 9; EC Metalloproteinase 14

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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