Circulation, Ahead of Print. BACKGROUND:Myocardial ischemia/reperfusion (I/R) injury is a common and severe clinical complication in patients with ischemic heart disease after reperfusion therapy.
Effective therapeutic strategies for myocardial I/R injury remain limited. Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation.
However, the mechanisms underlying ferroptosis in myocardial I/R injury are not fully understood.METHODS:Transcriptomic data from patients with heart failure and cardiomyocytes undergoing ferroptosis were analyzed. Based on the screening results, TRIM28 (tripartite motif-containing 28) expression was evaluated in ferroptotic cardiomyocytes.
Cardiac I/R injury models in mice and hypoxia/reoxygenation injury models in neonatal rat ventricular myocytes were established. To explore the function of TRIM28, we used adeno-associated virus serotype 9 to achieve cardiomyocyte-specific overexpression and generated tamoxifen-inducible cardiomyocyte–specific TRIM28 knockout mice.
RNA sequencing, coimmunoprecipitation coupled with mass spectrometry, and ubiquitinome profiling were applied to elucidate the underlying mechanisms. Human heart samples from patients with ischemic heart disease were used to evaluate the expression of TRIM28 and its related signaling molecules.
Circulation published a clinical update in Cardiology on 09 Mar 2026.
The item focuses on TRIM28 Is an E3 Ligase of IRP2 Suppressing Ischemia/Reperfusion–Induced Myocardial Ferroptosis.
Review the original article for the full source wording and details.