J Cardiovasc Transl Res. 2026 Jun 19;19(1):74. doi: 10.1007/s12265-026-10805-4.
ABSTRACT
Heart failure (HF) remains a major cause of morbidity and mortality, with ferroptosis increasingly implicated in its progression. Pim1, a serine/threonine kinase, exerts cardioprotective effects by regulating cell survival and oxidative stress, but its role in ferroptosis during HF remains unclear. Here, HF was induced in rats by left anterior descending coronary artery ligation, followed by lentiviral-mediated Pim1 overexpression. Cardiac function, myocardial injury, fibrosis, and ferroptosis-related markers were evaluated. In vitro, H9C2 cardiomyocytes were exposed to H2O2 or Erastin to model HF-related injury and ferroptosis. Pim1 overexpression significantly improved cardiac function, alleviated myocardial injury and fibrosis, and suppressed ferroptosis by reducing Fe²⁺, ROS, and lipid peroxidation while enhancing GSH and GPX4 activity. Mechanistically, Pim1 regulated the mTORC1/SLC7A11/GPX4 axis, whereas rapamycin abrogated these protective effects. Furthermore, the rescue experiments indicated that ferroptosis suppression is the primary mechanism of Pim1‑mediated protection. Collectively, Pim1 mitigates HF progression by inhibiting ferroptosis through mTORC1/SLC7A11/GPX4 signaling.
PMID:42319651 | DOI:10.1007/s12265-026-10805-4