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Differential expression of matrix metalloproteinases and tissue inhibitors and extracellular matrix remodeling in aortic regurgitant hearts.
Cardiology. 2009; 113(3):161-8.C

Abstract

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.

Authors+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19129699

Citation

Truter, Sharada L., et al. "Differential Expression of Matrix Metalloproteinases and Tissue Inhibitors and Extracellular Matrix Remodeling in Aortic Regurgitant Hearts." Cardiology, vol. 113, no. 3, 2009, pp. 161-8.
Truter SL, Catanzaro DF, Supino PG, et al. Differential expression of matrix metalloproteinases and tissue inhibitors and extracellular matrix remodeling in aortic regurgitant hearts. Cardiology. 2009;113(3):161-8.
Truter, S. L., Catanzaro, D. F., Supino, P. G., Gupta, A., Carter, J., Herrold, E. M., Dumlao, T. F., & Borer, J. S. (2009). Differential expression of matrix metalloproteinases and tissue inhibitors and extracellular matrix remodeling in aortic regurgitant hearts. Cardiology, 113(3), 161-8. https://doi.org/10.1159/000187723
Truter SL, et al. Differential Expression of Matrix Metalloproteinases and Tissue Inhibitors and Extracellular Matrix Remodeling in Aortic Regurgitant Hearts. Cardiology. 2009;113(3):161-8. PubMed PMID: 19129699.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential expression of matrix metalloproteinases and tissue inhibitors and extracellular matrix remodeling in aortic regurgitant hearts. AU - Truter,Sharada L, AU - Catanzaro,Daniel F, AU - Supino,Phyllis G, AU - Gupta,Anuj, AU - Carter,John, AU - Herrold,Edmund M, AU - Dumlao,Themy F, AU - Borer,Jeffrey S, Y1 - 2009/01/08/ PY - 2008/08/14/received PY - 2008/08/15/accepted PY - 2009/1/9/entrez PY - 2009/1/9/pubmed PY - 2009/8/14/medline SP - 161 EP - 8 JF - Cardiology JO - Cardiology VL - 113 IS - 3 N2 - 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. SN - 1421-9751 UR - https://www.unboundmedicine.com/medline/citation/19129699/Differential_expression_of_matrix_metalloproteinases_and_tissue_inhibitors_and_extracellular_matrix_remodeling_in_aortic_regurgitant_hearts_ L2 - https://www.karger.com?DOI=10.1159/000187723 DB - PRIME DP - Unbound Medicine ER -