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Macrolide antibiotics are broadly used for the treatment of various microbial infections. However, they are also known to have multiple biologic effects, such as alteration of inflammatory factors and matrix metalloproteinases (MMPs). Because of controversial results in clinical trials, the effects of macrolides on cardiovascular diseases are still to be elucidated. It has been reported that MMP activity is upregulated in various cardiovascular diseases, such as myocarditis, cardiac transplant rejection and myocardial infarction. However, little is known about the effects of macrolides on cardiovascular diseases. We have reported that clarithromycin suppressed the development of myocarditis, cardiac rejection and myocardial ischemia using animal models. In this article, we reviewed the roles of MMPs in cardiovascular diseases and the effects of macrolides on the prevention of adverse tissue remodeling., (© 2011 Blackwell Publishing Ltd.)

Objective: Amplification of inflammatory response in the non-infarct area plays an important role in the pathogenesis of ventricular remodeling after myocardial ischemia. Activation of nuclear factor-kappa B (NF-kappaB) is involved in this amplification through a positive feedback loop of pro- inflammatory cytokines. We investigated the efficacy of IKK blockade with IMD-0560, a novel inhibitor of IKK, in a rat myocardial ischemia model., Methods/results: Left coronary artery occlusion (28 days) was carried out in Sprague-Dawley rats. Daily intraperitoneal injections of IMD-0560 (5 mg/kg) were done after the operation. Treatment with IMD-0560 significantly improved cardiac function as indicated by the preservation of fractional shortening and lower serum brain natriuretic peptide level. Histological analysis showed that IMD-0560 treatment suppressed thinning in the infarcted area compared with vehicle-treated hearts. Moreover, in situ zymography showed matrix metalloprotease-9 activity was inhibited in the infarct area., Conclusion: We revealed that the IKK blockade is potent for the suppression of chronic ventricular remodeling after myocardial ischemia.

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. [ABSTRACT FROM AUTHOR]