| Matrix metalloproteinase (MMP)-9, but not MMP-2, is involved in the development and progression of C protein-induced myocarditis and subsequent dilated cardiomyopathy. | |
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MedLine Citation:
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PMID: 19734212 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Repeated or continuous inflammation of the heart is one of the initiation factors for dilated cardiomyopathy (DCM). In previous studies, we established a DCM animal model by immunizing rats with cardiac C protein. In the present study, we analyze the role of matrix metalloproteinases (MMPs) in experimental autoimmune carditis (EAC) and subsequent DCM to elucidate the pathomechanisms of this disease. In this model, inflammation begins approximately 9 days after immunization. At that time, MMP activities were detected by in situ zymography. Real-time PCR analysis revealed continuous up-regulation of MMP-2 mRNA from 2 wk and thereafter. MMP-9 mRNA, however, had only a transient increase at 2 wk. Double staining with in situ zymography and cell markers demonstrated that gelatinase (MMP-2 and MMP-9)-expressing cells are infiltrating macrophages during the early stage and cardiomyocytes at later stages. Minocycline, which inhibits MMP-9 activities more strongly than MMP-2, significantly suppressed EAC, but an MMP-2-specific inhibitor, TISAM, did not affect the course of the disease. Furthermore, immunohistochemical examination revealed that minocycline treatment suppressed T cell and macrophage infiltration strongly, whereas TISAM did not. These findings indicate that MMP-9, but not MMP-2, is involved in the pathogenesis of the acute phase of EAC, and further suggest that MMP-9 inhibitors, minocycline and its derivatives, may be useful therapies for EAC and DCM. |
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Authors:
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Yoh Matsumoto; Il-Kwon Park; Kuniko Kohyama |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-04 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 183 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-09-21 Completed Date: 2009-11-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 4773-81 Citation Subset: AIM; IM |
Affiliation:
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Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Musashidai 2-6, Fuchu, Tokyo 183-8526, Japan. matyoh@tmin.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autoimmune Diseases / drug therapy, enzymology, pathology Cardiomyopathy, Dilated / drug therapy, enzymology*, immunology, pathology Carrier Proteins / toxicity* Disease Progression Female Inflammation Mediators / physiology Male Matrix Metalloproteinase 2* / antagonists & inhibitors, biosynthesis, physiology Matrix Metalloproteinase 9 / antagonists & inhibitors, biosynthesis, physiology* Myocarditis / drug therapy, enzymology*, immunology, pathology Protease Inhibitors / therapeutic use Rats Rats, Inbred Lew |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Inflammation Mediators; 0/Protease Inhibitors; 0/myosin-binding protein C; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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