In this study, we provided direct evidence demonstrating that downregulating Meox1 suppressed CFs-to-Myofbs transition, alleviated pathological fibrosis and remodeling, and improved cardiac function in mice post-MI, primarily through inhibiting the collagen triple helix repeat containing 1 (Cthrc1)/p-Smad2/3 signaling pathway. This evidence concerns the gene MEOX1 and myocardial infarction.