Document Detail


Early treatment with clarithromycin attenuates rat autoimmune myocarditis via inhibition of matrix metalloproteinase activity.
MedLine Citation:
PMID:  20350988     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Matrix metalloproteinase (MMP) activity is upregulated in the hearts with myocarditis, and its activation contributes to the changes in left ventricular function. A major macrolide antibiotic, clarithromycin (CAM), has many biological functions including MMP regulation. However, little is known about the effect of CAM in myocarditis via MMPs. OBJECTIVE: To clarify the role of MMPs regulated by CAM in the progression of myocarditis. Design CAM was given to experimental rats with autoimmune myocarditis (EAM) from day -7 to day 21 (early treated group, n=6) or from day 1 to day 21 (late treated group, n=6) twice a day. RESULTS: Although the non-treated rats showed blood pressure decline and impaired cardiac function, early CAM treatment prevented this progression. Pathologically, severe myocardial cell infiltration (30.5+/-4.2%) and fibrosis (32.2+/-1.1%) were detected in the non-treated group, while early CAM treatment significantly suppressed these changes (infiltration 6.5+/-0.2%, fibrosis 5.9+/-3.9%). Zymography showed that non-treated EAM resulted in enhanced ventricular activities of MMP-9, while early CAM treatment reduced the alteration. However, late CAM treatment was less effective than the early treatment. CONCLUSIONS: Early CAM treatment is effective to attenuate myocarditis by suppressing MMP-9.
Authors:
Keiichi Hishikari; Ryo Watanabe; Masahito Ogawa; Jun-ichi Suzuki; Mayumi Masumura; Tomoko Shimizu; Kiyoshi Takayama; Yasunobu Hirata; Ryozo Nagai; Mitsuaki Isobe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Heart (British Cardiac Society)     Volume:  96     ISSN:  1468-201X     ISO Abbreviation:  Heart     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-30     Completed Date:  2010-06-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9602087     Medline TA:  Heart     Country:  England    
Other Details:
Languages:  eng     Pagination:  523-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Advanced Clinical Science and Therapeutics, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan. junichisuzuki-circ@umin.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Autoimmune Diseases / drug therapy*
Blood Pressure / drug effects
Clarithromycin / pharmacology*
Heart Rate / drug effects
Immunohistochemistry
Male
Matrix Metalloproteinases / antagonists & inhibitors*
Myocardial Contraction / drug effects
Myocarditis / drug therapy*
Protein Synthesis Inhibitors / pharmacology*
Rats
Rats, Inbred Lew
Chemical
Reg. No./Substance:
0/Protein Synthesis Inhibitors; 81103-11-9/Clarithromycin; EC 3.4.24.-/Matrix Metalloproteinases
Comments/Corrections
Comment In:
Heart. 2010 Apr;96(7):494-5   [PMID:  19617212 ]

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