Myocardial infarction with a pathogenic basis of thrombosis or vascular occlusion remains a global medical concern characterized by high morbidity and mortality(Peet et al., 2020). Fine-tuning the inflammatory cascade is vital in post-infarction myocardial repair and remodeling(Niccoli et al., 2018; Contessotto et al., 2023; Santos-Zas et al., 2018).

Resolution of inflammation is a self-restraining process in part mediated by specialized pro-solving mediators (SPMs) to antagonize against inflammation (Peet et al., 2020). Defects in SPM metabolism are common in inflammatory-related diseases (Jadapalli and Halade, 2018; Li et al., 2020). As a subdivision of SPM, maresin2 is bio-synthesized from the long-chain n-3 polyunsaturated fatty acid—docosahexaenoic acid (DHA) with the mediation of 12-lipoxygenase (12-LOX) (Yao and Lv, 2022). DHA is catabolized into a 14-hydroperoxide intermediate, which acts as the substrate for enzymatic epoxidation into the 13S, 14S-epoxy-maresin. Manifested by different hydrolysis entrances, 13S, 14S-epoxy-maresin is catabolized into maresin-1 (via enzymatic hydrolysis) or maresin2 (via soluble epoxide hydrolase) (Hwang et al., 2019; Lopez-Vicario et al., 2023). While the biological actions of maresin-1 on the heart have been extensively documented, maresin2 is a newcomer largely unknown.

Macro-autophagy (hereafter autophagy) is a cellular degradative process pivotal in the assembly of autophagosomes comprising cytoplasm or membrane-localized organelles and cellular debris. Autophagosomes are sequestered by cargo structure into lysosome in a fusion manner for bulk recycling of cellular components (Schlotawa et al., 2023). In mammalian autophagy, Unc-51–like autophagy activating kinase (ULK1) complex plays as a core autophagy initiating machinery that connects cargo recognition with isolation membrane biogenesis and elongation of nucleated autophagosome (Ren et al., 2023; Schlotawa et al., 2023). There are four proteins to form the ULK1 complex: ULK1 kinase, autophagy-related 13 (ATG13), autophagy-related 101 (ATG101), and focal adhesion kinase family interacting protein of 200 kDa (FIP200) (Egan et al., 2015; Ganley et al., 2009; Mercer et al., 2009). These complexes and proteins, as early-packed autophagosome, underpin debris cargo identification, autophagosome closure, and fusion with lysosomes, which is called autophagic flux (Ren et al., 2023; Stanley et al., 2014; Zhang et al., 2023; Zhong et al., 2023).

O-GlcNAcylation, a posttranslational modification process that attaches O-linked β-N-acetylglucosamine (O-GlcNAc) moieties on serine/threonine residues, is regulated by O-GlcNAc transferase (OGT) catalyzing the incorporation of β-O-GlcNAc from the donor substrate uridine-5′-diphospho-N-acetylglucosamine (UDP-GlcNAc) and O-GlcNAcase (OGA) catalyzing the removal of O-GlcNAc from the glycosylated substrates (Hanover et al., 2012; Hart et al., 2007). Glucose, glutamine, and glucosamine are substrates for the hexosamine biosynthetic pathway (HBP) deriving UDP-GlcNAc (Lv et al., 2022). Baseline HBP routine utilizes 2∼5% total glucose and is mainly modulated by glucose/glutamine supply amount, and the rate-limiting enzyme is glutamine-fructose-6-phosphate amidotransferases (GFATs) (Hart, 2013; Yang and Qian, 2017). GFATs convert fructose-6-phosphate and glutamine to glucosamine-6-phosphate (GlcN-6-P), the precursor of UDP-GlcNAc (Wang et al., 2018; Yu et al., 2020). Aberrant HBP in the heart has been implicated in orchestrating cardiac cell fate from cues of glucose, fatty acid, and amino acid nutritious properties (Dassanayaka et al., 2017). Furthermore, cardiac GFAT activity with putative function on the nucleus factor pathway might be regulated by the inflammation cascade. That nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling to interact with GFAT1 in a fine-tuned manner promotes autophagy by recruitment of downstream p38 mitogen-activated protein kinase (p38 MAPK) (Wei et al., 2022). If maresin2 could be involved in cardiac repair and remodeling, elucidating its underlying mechanism helps provide theoretical rationality of maresin2 for myocardial treatment.