Functional assays demonstrated that sarcosine, pyroglutamic acid, and 3-hydroxypropionic acid modulate the gene expression of cardiac regenerative biomarkers, including GATA4, Nkx2.5, TROP-I, LGALS1, TBX5, and IRX4.<h4>Conclusions</h4>These findings suggest that ischemia-induced metabolomic changes exert transcriptional control over cardiac remodeling programs, emphasizing the regulatory potential of metabolite-gene interactions. Here, NKX2-5 is linked to ischemia.