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  • Early treatment with clarithromycin attenuates rat autoimmune myocarditis via inhibition of matrix metalloproteinase activity

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Myocarditis
Early treatment with clarithromycin attenuates rat autoimmune myocarditis via inhibition of matrix metalloproteinase activity
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  1. Keiichi Hishikari1,
  2. Ryo Watanabe2,
  3. Masahito Ogawa2,
  4. Jun-ichi Suzuki2,
  5. Mayumi Masumura1,
  6. Tomoko Shimizu3,
  7. Kiyoshi Takayama3,
  8. Yasunobu Hirata2,
  9. Ryozo Nagai4,
  10. Mitsuaki Isobe1
  1. 1Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
  2. 2Department of Advanced Clinical Science and Therapeutics, University of Tokyo, Bunkyo, Tokyo, Japan
  3. 3NB Health Laboratory, Kawaguchi, Saitama, Japan
  4. 4Department of Cardiovascular Medicine, University of Tokyo, Bunkyo, Tokyo, Japan
  1. Correspondence to Professor Jun-ichi Suzuki, Department of Advanced Clinical Science and Therapeutics, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan; junichisuzuki-circ{at}umin.ac.jp

Abstract

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.

  • Myocarditis
  • inflammation
  • macrolide
  • matrix metalloproteinases
  • myocardial remodelling

https://doi.org/10.1136/hrt.2009.188094

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    Footnotes

    • Linked articles 173740.

    • Funding This study was supported by grants from a Grant-in-aid from the Japan Society for the Promotion of Science.

    • Competing interests None.

    • Patient consent Obtained.

    • Provenance and peer review Not commissioned; not externally peer reviewed.

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