Fibroblast Growth Factor 21 Protects Against Atrial Remodeling via Reducing Oxidative Stress

Abstract

Aim: The structural and electrical changes in the atrium, also known as atrial remodeling, are the main characteristics of atrial fibrillation (AF). Fibroblast growth factor 21 (Fgf21) is an important endocrine factor, which has been shown to play an important role in cardiovascular diseases. However, the effects of Fgf21 on atrial remodeling have not been addressed yet. The purpose of the present study is to evaluate the effects of Fgf21 on atrial remodeling.Methods and Results: Adult mice were treated with Ang II, and randomly administrated with or without Fgf21 for 2 weeks. The susceptibility to AF was assessed by electrical stimulation and optical mapping techniques. Here, we found that Fgf21 administration attenuated the inducibility of atrial fibrillation/atrial tachycardia (AF/AT), improved epicardial conduction velocity in the mice atria. Mechanistically, Fgf21 protected against atrial fibrosis and reduced oxidative stress of the atria. Consistently, in vitro study also demonstrated that Fgf21 blocked the upregulation of collagen by Tgf-β in fibroblasts and attenuated tachypacing-induced oxidative stress including reactive oxygen species (ROS), Tgf-β, and ox-CaMKII in atrial myocytes. We further found that Fgf21 attenuated oxidative stress by inducing antioxidant genes, such as SOD2 and UCP3. Fgf21 also improved tachypacing-induced myofibril degradation, downregulation of L-type calcium channel, and upregulation of p-RyR2, which implicated protective effects of Fgf21 on structural and electrical remodeling in the atria. Moreover, Nrf2 was identified as a downstream of Fgf21 and partly mediated Fgf21-induced antioxidant gene expression in atrial myocytes.Conclusion: Fgf21 administration effectively suppressed atrial remodeling by reducing oxidative stress, which provides a novel therapeutic insight for AF.

FGF21 improves ventricular remodeling in TAC induced heart failure rats

“…Then, we used rmFGF21 to signi cantly improve cardiac echocardiography and serological indexes after overexpression of FGF21 in HF models, suggesting a signi cant improvement in cardiac function, and further veri ed the cardiac protective effect of FGF21 in HF. This is consistent with the conclusions reported in the literature, which found that FGF21 can improve the function of failing heart by increasing LVEF and LVFS and decreasing serum BNP levels [19,20] .…”

Elevated serum FGF21 levels predict heart failure during hospitalization of STEMI patients after emergency percutaneous coronary intervention

“…It was found that the cardioprotective effect of FGF21 was limited due to its low expression in the normal heart ( Chen et al, 2021 ). Once the heart is exposed to multiple stimuli such as ischemia and hypoxia, inflammation, oxidative stress, lipotoxicity and endoplasmic reticulum stress, the secretion of FGF21 is significantly increased to fully play a cardioprotective role ( Planavila et al, 2013a ; Planavila, Redondo-Angulo & Villarroya, 2015 ).…”

Identification of Differentially Expressed Genes and Pathways in Human Atrial Fibrillation by Bioinformatics Analysis

“…Chen M found that by increasing antioxidant genes such as SOD2 and UCP3, fibroblast growth factor 21 successfully reduced atrial remodeling by lowering oxidative stress. 46 In addition, Wang et al revealed that CXCR4 expression is increased in chronic AF patients with mitral valve dysfunction, that it is related with atrial remodeling. 47 However, no difference in the expression of PDK4, S100A12, RASD1, or DDIT4 was seen between AF patients and HCs.…”