Disulfidptosis occurs in early stage of Myocardial Infarction: A Novel Pathological Mechanism of cardiac dysfunction

Myocardial infarction (MI) is one of the leading causes of death in cardiovascular diseases. Disulfidptosis is a newly discovered form of programmed cell death in recent years. However, whether disulfidptosis occurs during MI still remains unclear. This study mainly investigates the occurrence of disulfidptosis in cardiomyocytes post-MI and its impact on cardiac function. MI models were established using C57BL/6J wild-type (WT) mice. RNA sequencing results of heart tissues from MI mice were collected for bioinformatics analysis. Western blotting, fluorescent staining and other molecular techniques were used to detect the changes of disulfidptosis-related molecules SLC7A11 and glucose transporter GLUT1, as well as the trailing of cytoskeletal proteins FLNA and DREBRIN and the contraction of f-actin. Bioinformatics analysis showed that the expression of key disulfidptosis molecules such as slc7a11 was increased and disulfidptosis-related signaling pathways were activated in infarcted heart tissues post-MI. Western blotting confirmed the upregulation of SLC7A11 in infarcted myocardium of mice. Non-reducing Western blotting revealed slower migration of cytoskeletal proteins, and fluorescent staining showed F-actin contraction in the infarct hearts. The in vitro data showed that mouse cardiomyocytes died and their cytoskeletons contracted with upregulation of slc7a11 under glucose-free or hypoxic conditions. The cytoskeletal changes were alleviated by adding 2-me and 2-dg, and significantly aggravated when cells were exposed to glucose-free and hypoxic environments. Preoperative and postoperative administrations of slc7a11 inhibitor hg-106 to MI mice could markedly mitigate cardiac function decline, while administration GLUT1 inhibitor bay-876 further exacerbated this decline. This study demonstrates an occurrence of disulfidptosis during the early stage of MI in the mice, and intervening disulfidptosis can improve cardiac function of the model mice.