Importantly, β-Catenin knockdown abrogates Ube2s-augmented HIF-1α activation, and meanwhile, diminishes the protective effect of Ube2s on MI/R injury, thus establishing a causal link between Ube2s-stabilized β-catenin and HIF-1α-mediated myocardial protection. Here, HIF1A is linked to myocardial infarction.