Maresin 1 promotes resolution of inflammation and improves left ventricle function in acute heart failure

The leukocyte-mediated innate inflammatory response is crucial for clearing ischaemic debris during myocardial infarction (MI). If unresolved, it leads to chronic inflammation and heart failure. While macrophages produce specialised pro-resolving mediators (SPMs) like maresin 1, the therapeutic potential of exogenous maresin 1 in cardiac repair remains unclear.

Male C57BL/6J mice (8-12 weeks) subjected coronary artery ligation to induce MI. Mice received either low-dose (LD; 0.4 μg kg^-1) or high-dose (HD; 4 μg kg^-1) maresin 1 subcutaneously 3 h post-MI, continued through day 1 or day 5. Saline-injected mice served as MI controls, while non-infarcted mice were used as naïve controls.

LD-maresin 1 enhanced neutrophil clearance but did not improve cardiac function. However, HD-maresin 1 significantly improved cardiac performance, evidenced by higher fractional shortening and global longitudinal strain, and reducing LV and lung mass-to-body weight ratios. In infarcted myocardium, HD-maresin 1 up-regulated FPR2 receptor expression and increased levels of SPMs (RvD5, PD-1, maresin 1). Flow cytometry showed accelerated neutrophil clearance from the LV and spleen. Moreover, HD-maresin 1 also promoted a reparative macrophage phenotype, with expansion of Ly6C^lo cells and up-regulation of Mrc1 and Arg1. Furthermore, kidney immunohistochemistry showed reduced NGAL and increased nephrin expression, indicating attenuation of cardiorenal inflammation.

High-dose maresin 1 activates FPR2 signalling and enhances the resolution of inflammation by modulating leukocyte dynamics and macrophage phenotype. Improving cardiac function and attenuating cardiorenal inflammation, highlighting the therapeutic potential of maresin 1 in cardiac healing and acute heart failure.