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

Background and Purpose 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. Experimental Approach 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. Key Results 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. Conclusions and Implications 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.