Lacylation of Stearoyl-CoA Desaturase-1 Contributes to the Myocardial Ischemia-Reperfusion Injury Through Regulating Wnt/β-Catenin Signaling.

Myocardial ischemia-reperfusion injury (MIRI) involves tissue damage following restoration of blood flow. Stearoyl-CoA desaturase 1 (SCD1), associated with metabolic disorders, may contribute to MIRI. This study investigated the mechanism of SCD1 in MIRI. A rat ischemia/reperfusion (I/R) model was established by ligating the left anterior descending coronary artery. The hypoxia/reoxygenation (H/R) model was used to simulate in vitro I/R. 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry were performed for histopathological analysis of rat heart tissues. The ferroptosis indicators were detected using commercial kits and Western blot. Lactylation and ubiquitination of SCD1 were detected by Western blot. I/R increased tissue damage and SCD1 expression. In addition, SCD1 inhibition attenuated ferroptosis in H/R cells and I/R hearts. H/R induced ferroptosis via promoting lactylation modification in H9c2 cells. Mechanistically, lactylation of SCD1 at K208 stabilized its protein stability and activated Wnt/β-Catenin signaling to promote ferroptosis in H9c2 cells. In vivo, SCD1 silencing inhibited the MIRI. SCD1 lactylation drove ferroptosis in MIRI by regulating Wnt/β-Catenin signaling, offering potential therapeutic insights.