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

Cardiovascular Therapeutics
Wei GongShaoping Nie

Abstract

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. MI models were induced by left coronary artery ligation in male C57BL/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 (MMPs) were analyzed by Western Blotting. 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 H2 O2 and found that TMZ treatment markedly decreased H2 O2 -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. Our findings indicate that T...Continue Reading

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Citations

Mar 6, 2021·Heliyon·Isabel Cristina Celerino de Moraes PortoJohnnatan Duarte de Freitas
Apr 4, 2021·Biomolecules·Mediha Becirovic-AgicMerry L Lindsey
Nov 13, 2021·Clinical and Experimental Pharmacology & Physiology·Marwa MedhetEbtehal El-Demerdash

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