mRNA-103 inhibition attenuates autophagy and inflammation in myocardial infarction by regulating the TLR4 pathway

Abstract

Introduction: This investigation determined the cardioprotective activity of mRNA-103 inhibitor against myocardial infarction (MI) and also evaluated its molecular mechanism. Material and methods: MI was induced in rats by inducing myocardial ischaemia/reperfusion (I/R), and left ventricular (LV) mRNA-103 (1 × 10 7 TU) was injected into the myocardium around the infarcted area. The effect of mRNA-103 inhibitor was assessed by determining the levels of myocardial enzymes and cytokines in the serum, the myeloperoxidase (MPO) activity, and the levels of Toll-like receptor 4 (TLR4), nuclear factor k-light-chain enhancer of activated B cells (NF-kB), and MyD88 mRNAs in the myocardial tissues of MI rats. Immunocytochemical analysis and a histopathology study were also performed. Results: The levels of myocardial enzymes and cytokines were lower in the mRNA-103 inhibitor-treated group than in the group in which the only treatment was the induction of MI. There was a lower percentage of infarcted area and a lower apoptosis index in the mRNA-103 inhibitor-treated group compared to the MI-only. The levels of TLR4, NF-kB, and MyD88 mRNAs were lower in the myocardial tissues of the mRNA-103 inhibitor-treated group than in the MI-only group. Immunohistochemical analysis revealed that treatment with mRNA-103 inhibitor ameliorated the expression of TLR4 in the myocardial tissues of MI rats. Conclusions: The data revealed that inhibition by mRNA-103 protects against myocardial injury in MI rats by regulating the inflammasome pathway.