• Diabetic cardiomyopathy (DCM) is associated with ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation.
• HMOX1 is upregulated in DCM and its knockdown alleviates ferroptosis, reducing cardiac fibrosis and improving cardiac function.
• The study provides evidence that targeting HMOX1-mediated ferroptosis could be a novel therapeutic strategy for DCM.
• Both in vivo and in vitro models confirm that the diabetic microenvironment induces ferroptosis, with key markers altered (GPX4, SLC7A11, ferritin, PTGS2, ACSL4).