Early treatment with clarithromycin attenuates rat autoimmune myocarditis via inhibition of matrix metalloproteinase activity.
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.
Hishikari
Keiichi
K
Department of Advanced Clinical Science and Therapeutics, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan. junichisuzuki-circ@umin.ac.jp
Watanabe
Ryo
R
Ogawa
Masahito
M
Suzuki
Jun-ichi
J
Masumura
Mayumi
M
Shimizu
Tomoko
T
Takayama
Kiyoshi
K
Hirata
Yasunobu
Y
Nagai
Ryozo
R
Isobe
Mitsuaki
M
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D017291:Clarithromycin / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D009200:Myocardial Contraction / Q000187:drug effects; D009205:Myocarditis / Q000188:drug therapy*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew
D061965:Matrix Metalloproteinase Inhibitors; D011500:Protein Synthesis Inhibitors; D017291:Clarithromycin