Figure 8.

Myocardial ischemia induces 4‐HNE accumulation and GPX4 reduction in human samples. A) Immunoblots of 4‐HNE and GPX4 proteins in the right auricle from control patients and patients with ischemia (n = 6). B) Representative immunohistochemical staining of the control and ischemic patients (n = 4). Scale bar:50 µm. C) Schematic illustration of 4‐HNE‐induced ferroptosis in myocardial ischemia‐reperfusion. At basal conditions, OTUD5 deubiquitinates and stabilizes GPX4. In myocardial ischemia/reperfusion, 4‐HNE binds competitively to OTUD5 and GPX4, blocks the interaction between OTUD5 and GPX4, and promotes GPX4 ubiquitination and degradation, which induces ferroptosis and aggravates myocardial injury. Data are expressed as mean ± SEM. Unpaired two‐tailed Student's t‐test was used for the analysis in A,B).