Maresin1 ameliorates ventricular remodelling and arrhythmia in mice models of myocardial infarction via NRF2/HO-1 and TLR4/NF-kB signalling.

Abstract

Ventricular remodelling and arrhythmias are the main factors that affect the quality of life of patients with myocardial infarction (MI). Maresin 1 (Mar1) is associated with antioxidative and anti-inflammatory effects. However, the mechanisms underlying the effects of Mar1 in MI remain unclear. In this study, we aimed to explore the role and potential mechanisms of Mar1 in a mouse model of MI. The mice were divided into four groups: Sham, Sham+Mar1, MI, and MI+Mar1. In the MI groups, the left anterior descending coronary artery of the mice was ligated for 28days, while this ligation was not conducted in the Sham groups. Mar1 was injected into mice in the Sham+Mar1 and MI+Mar1 groups. H9c2 cells were cultured in vitro under hypoxic conditions for MI models, and then Mar1 was added to the medium for 24h. Our data demonstrated that Mar1 activated NRF2/HO-1 signalling and inhibited TLR4/NF-kB signalling in MI. These activities lead to inhibition of the release of inflammatory cytokines, reduction of myocardial apoptosis and interstitial fibrosis, decreased susceptibility to ventricular arrhythmias, and improved cardiac function. Similarly, our in vitro analyses showed that Mar1 inhibited inflammatory signalling by enhancing the antioxidative function of NRF2/HO-1 signalling. Furthermore, Mar1 inhibited hypoxia-activated apoptosis in cardiomyocytes. Taken together, our data demonstrate that Mar1 ameliorates ventricular remodelling and arrhythmias in mice post-MI via the activation of NRF2/HO-1 signalling and inhibition of the TLR4/NF-kB signalling pathways.