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01.03.2020 | Original Contribution

Fibroblast growth factor 21 inhibited ischemic arrhythmias via targeting miR-143/EGR1 axis

verfasst von: Jiamin Li, Chaoqian Xu, Yining Liu, Yuanshi Li, Sijia Du, Ruijie Zhang, Yuehang Sun, Ronghao Zhang, Ying Wang, Hongru Xue, Sha Ni, Mavlikhanova Asiya, Genlong Xue, Yanyao Li, Ling Shi, Desheng Li, Zhenwei Pan, Yong Zhang, Zhiguo Wang, Benzhi Cai, Ning Wang, Baofeng Yang

Erschienen in: Basic Research in Cardiology | Ausgabe 2/2020

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Abstract

Ventricular arrhythmia is the most common cause of sudden cardiac death in patients with myocardial infarction (MI). Fibroblast growth factor 21 (FGF21) has been shown to play an important role in cardiovascular and metabolic diseases. However, the effects of FGF21 on ventricular arrhythmias following MI have not been addressed yet. The present study was conducted to investigate the pharmacological action of FGF21 on ventricular arrhythmias after MI. Adult male mice were administrated with or without recombinant human basic FGF21 (rhbFGF21), and the susceptibility to arrhythmias was assessed by programmed electrical stimulation and optical mapping techniques. Here, we found that rhbFGF21 administration reduced the occurrence of ventricular tachycardia (VT), improved epicardial conduction velocity and shorted action potential duration at 90% (APD₉₀) in infarcted mouse hearts. Mechanistically, FGF21 may improve cardiac electrophysiological remodeling as characterized by the decrease of I_Na and I_K1 current density in border zone of infarcted mouse hearts. Consistently, in vitro study also demonstrated that FGF21 may rescue oxidant stress-induced dysfunction of I_Na and I_K1 currents in cultured ventricular myocytes. We further found that oxidant stress-induced down-regulation of early growth response protein 1 (EGR1) contributed to I_Na and I_K1 reduction in post-infarcted hearts, and FGF21 may recruit EGR1 into the SCN5A and KCNJ2 promoter regions to up-regulate Na_V1.5 and Kir2.1 expression at transcriptional level. Moreover, miR-143 was identified as upstream of EGR1 and mediated FGF21-induced EGR1 up-regulation in cardiomyocytes. Collectively, rhbFGF21 administration effectively suppressed ventricular arrhythmias in post-infarcted hearts by regulating miR-143-EGR1-Na_V1.5/Kir2.1 axis, which provides novel therapeutic strategies for ischemic arrhythmias in clinics.

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Titel: Fibroblast growth factor 21 inhibited ischemic arrhythmias via targeting miR-143/EGR1 axis
verfasst von: Jiamin Li
Chaoqian Xu
Yining Liu
Yuanshi Li
Sijia Du
Ruijie Zhang
Yuehang Sun
Ronghao Zhang
Ying Wang
Hongru Xue
Sha Ni
Mavlikhanova Asiya
Genlong Xue
Yanyao Li
Ling Shi
Desheng Li
Zhenwei Pan
Yong Zhang
Zhiguo Wang
Benzhi Cai
Ning Wang
Baofeng Yang
Publikationsdatum: 01.03.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Basic Research in Cardiology / Ausgabe 2/2020
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-019-0768-4

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Fibroblast growth factor 21 inhibited ischemic arrhythmias via targeting miR-143/EGR1 axis

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