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

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.