J Cardiovasc Transl Res. 2025 Oct 2. doi: 10.1007/s12265-025-10707-x. Online ahead of print.
ABSTRACT
This study aimed to investigate the underlying mechanisms of Fibroblast Growth Factor 21 (FGF21) in myocardial ischemia/reperfusion (I/R) injury. First, FGF21 was upregulated in the serum of patients with myocardial I/R injury as well as in I/R hearts of mice and hypoxia/reoxygenation (H/R) neonatal rat cardiomyocytes (NRCMs). While FGF21 knockout exacerbated such injury, which was mitigated by rhFGF21. Bioinformatics analysis identified immunity-related GTPase M1 (Irgm1) as a key autophagy-related gene downregulated in ventricular tissue of FGF21-/- I/R mice. Impaired autophagic flux in FGF21-/- mice during I/R could be rescued by rhFGF21 through the signal transducers and activators of transcription 1 (STAT1) pathway. The beneficial effects of rhFGF21 in reducing H/R injury were limited in Irgm1 knockdown NRCMs. This study suggested that FGF21 deficiency intensifies myocardial I/R injury by exacerbating the impairment of autophagic flux. Activation of FGF21 or Irgm1 may serve as a promising therapeutic strategy for myocardial I/R injury.
PMID:41037149 | DOI:10.1007/s12265-025-10707-x
