Trimetazidine suppresses oxidative stress, inhibits MMP ‐2 and MMP ‐9 expression, and prevents cardiac rupture in mice with myocardial infarction

Summary Background/Aims Cardiac rupture ( CR ) is a catastrophic complication of acute myocardial infarction ( MI ). At present, there are no effective pharmacological strategies for preventing post‐ MI rupture. Here we investigated the effect of trimetazidine ( TMZ ) on post‐ MI CR . Methods MI models were induced by left coronary artery ligation in male C57 BL /6 mice. Animals allocated to the rupture incidence were closely monitored for 7 days; autopsy was performed once animals were found dead to determine the reason of death. Heart function was detected by echocardiography. Oxidative stress markers and matrix metalloproteinases ( MMP s) were analyzed by Western Blotting. Results TMZ markedly reduced the post‐ MI CR incidence of mice. We found that the expression of metalloproteinase ( MMP ) ‐2 and MMP ‐9 in the TMZ ‐treated group was significantly lower than the saline‐treated group. Further, TMZ markedly attenuated MI ‐induced oxidative stress. To investigate the mechanism of the effect of TMZ on CR , we pretreated H9c2 cells with H 2 O 2 and found that TMZ treatment markedly decreased H 2 O 2 ‐induced MMP ‐2 and MMP ‐9 expression. TMZ prevents CR through inhibition of oxidative stress, which is attributable to the down‐regulation of MMP ‐2, MMP ‐9 expression. Conclusions Our findings indicate that TMZ suppresses oxidative stress, inhibits MMP ‐2 and MMP ‐9 expression, and prevents CR in mice with MI .