FGF21 inhibited NETs formation induced by myocardial I/R injury via AMPK

Background Previous investigations have established the anti-inflammatory properties of fibroblast growth factor 21 (FGF21). However, the specific mechanism through which FGF21 mitigates myocardial ischemia/reperfusion (I/R) injury by inhibiting neutrophil extracellular traps(NETs) formation remains unclear. Methods A mice model of myocardial I/R injury was induced, and myocardial tissue was stained with immunofluorescence to assess the formation of NETs. Serum NETs levels were quantified using a PicoGreen kit. In addition, the expression levels of AMP-activated protein kinase (AMPK) and FGF21 were evaluated by Wes fully automated protein blotting quantitative analysis system. Moreover, an hypoxia/reoxygenation (H/R) model was established using AMPK inhibitor and agonist pretreated H9c2 cells to further explore the relationship between FGF21 and AMPK. Results Compared with the control group, serum NETs levels were significantly higher in I/R mice, and a large number of NETs were formed in myocardial tissues (97.63±11.45 vs 69.65±3.33, P<0.05). However, NETs levels were reversed in FGF21 pretreated mice (P<0.05). Further studies showed that FGF21 enhanced AMPK expression, which was significantly increased after inhibition of AMPK and decreased after promotion of AMPK (P<0.05). Conclusions FGF21 may exert cardioprotective effects by inhibiting I/R injury-induced NETs formation via AMPK.