SLC1A5 mediates myocardial damage after myocardial infarction by triggering cardiomyocyte ferroptosis.

Myocardial infarction (MI) has become a major disease that causes significant global mortality. Notably ferroptosis may exert a key effect on myocardial injury after MI. As the glutamine transporter on the cell membrane, solute carrier family 1 member 5 (SLC1A5) plays a role as a ferroptosis-inducing gene and has a mediating effect on cell ferroptosis. However, whether SLC1A5 is involved in mediating cardiomyocyte ferroptosis and myocardial injury after MI remains to be further elucidated. In the present study, we investigated whether SLC1A5 mediated myocardial injury after MI by triggering cardiomyocyte ferroptosis in vivo and in vitro. Based on our findings, SLC1A5 exhibited crucial mediating effects on post-MI cardiomyocyte ferroptosis and myocardial injury, and these effects were stimulated by SLC1A5 overexpression, but inhibited by ferrostatin-1 (a ferroptosis inhibitor)and V9302 (a SLC1A5 inhibitor). In conclusion, our results revealed a novel molecular mechanism of ferroptosis regulated by SLC1A5, which is essential for cardiomyocyte ferroptosis pathogenesis and myocardial injury post-MI.