Fibroblast growth factor-21 as a novel metabolic factor for regulating thrombotic homeostasis (Li et al, 2022)

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Fibroblast growth factor-21 as a novel metabolic factor for regulating thrombotic homeostasis
Shuai Li, Haibo Jia, Zhihang Liu, Nan Wang, Xiaochen Guo, Muhua Cao, Fang Fang, Jiarui Yang, Junyan Li, Qi He, Rui Guo, Teng Zhang, Kai Kang, Zongbao Wang, Shijie Liu, Yukai Cao, Xinghao Jiang, Guiping Ren, Kai Wang, Bo Yu, Wei Xiao, Deshan Li

Fibroblast growth factor-21 (FGF-21) performs a wide range of biological functions in organisms. Here, we report for the first time that FGF-21 suppresses thrombus formation with no notable risk of bleeding. Prophylactic and therapeutic administration of FGF-21 significantly improved the degree of vascular stenosis and reduced the thrombus area, volume and burden.

We determined the antithrombotic mechanism of FGF-21, demonstrating that FGF-21 exhibits an anticoagulant effect by inhibiting the expression and activity of factor VII (FVII). FGF-21 exerts an antiplatelet effect by inhibiting platelet activation. FGF-21 enhances fibrinolysis by promoting tissue plasminogen activator (tPA) expression and activation, while inhibiting plasminogen activator inhibitor 1 (PAI-1) expression and activation. We further found that FGF-21 mediated the expression and activation of tPA and PAI-1 by regulating the ERK1/2 and TGF-β/Smad2 pathways, respectively. In addition, we found that FGF-21 inhibits the expression of inflammatory factors in thrombosis by regulating the NF-κB pathway.

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