FGF21 improves ventricular remodeling in TAC induced heart failure rats

Abstract Background: Studies have found that elevated serum fibroblast growth factor 21 (FGF21) levels in patients with heart failure (HF) predicted poor prognosis. While preclinical studies have found that FGF21 plays a favorable role in the pathophysiological process of heart failure. Clinically, this increase in serum FGF21 seems to contradict the results of preclinical studies, therefore, the purpose of this study was to analyze whether FGF21 can improve ventricular remodeling in the HF rats, thereby improving cardiac function. Methods: The HF model of transverse aortic coarctation (TAC) was conducted and divided into 4 groups: sham group (Sham), TAC model group (TAC), TAC+FGF21 neutralizing antibody (FGF21nAb) group (TAC+FGF21nAb), and TAC+FGF21nAb+recombinant mouse FGF21 (rmFGF21) group (TAC+FGF21nAb+rmFGF21). Echocardiography, hematoxylin-eosin staining (HE), Masson staining, enzyme linked immunosorbent assay (ELISA) and western blot (WB) were used to evaluate the changes of cardiac structure and function in each group. The adenosine triphosphate (ATP) in myocardial tissue was determined by colorimetry. The level of reactive oxygen species (ROS) in myocardial tissue was determined by chemiluminescence method. Results: Serum FGF21 level in the TAC+FGF21nAb group was significantly lower than that in the TAC group (29.42±8.54pg/ml vs1886.65±169.51 pg/ml, P<0.001). Compared with the Sham group, left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS)were significantly decreased (P<0.001), with a significant increase in serum B-type natriuretic peptide (BNP) levels (P<0.05) in the TAC group and TAC+FGF21nAb group. However, after 3 weeks of rmFGF21 treatment, LVEF and LVFS were significantly increased (P<0.001), and serum BNP was significantly decreased (P<0.001). Compared to the Sham group, the heart mass significantly increased (P<0.01), myocardial cell hypertrophy, inflammatory cell infiltration，a large amount of fiber deposits in myocardium and around blood vessels, ROS level significantly increased (P<0.001), and the ATP content was significantly decreased (P<0.001) were observed in the TAC group and TAC+FGF21nAb group. While rmFGF21 could improve the above phenomenon. Conclusion: FGF21 can improve ventricular remodeling and cardiac function in HF rats by anti-inflammation, anti-fibrosis, reducing oxidative stress and regulating energy metabolism.