FGF21 mitigates atherosclerosis via inhibition of NLRP3 inflammasome-mediated vascular endothelial cells pyroptosis

Zhaolin Zeng; Qiuping Zheng; Jiaojiao Chen; Xianhua Tan; Qiang Li; Lingxin Ding; Ren Zhang; Xiaolong Lin

doi:10.1016/j.yexcr.2020.112108

FGF21 mitigates atherosclerosis via inhibition of NLRP3 inflammasome-mediated vascular endothelial cells pyroptosis

Exp Cell Res. 2020 Aug 15;393(2):112108. doi: 10.1016/j.yexcr.2020.112108. Epub 2020 May 20.

Authors

Zhaolin Zeng¹, Qiuping Zheng², Jiaojiao Chen³, Xianhua Tan², Qiang Li², Lingxin Ding², Ren Zhang², Xiaolong Lin⁴

Affiliations

¹ Department of Cardiology, Nanchuan People's Hospital, Chongqing Medical University, Chongqing, 408499, China; Key Lab for Atherosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang, 421001,China.
² Department of Cardiology, Nanchuan People's Hospital, Chongqing Medical University, Chongqing, 408499, China.
³ Key Lab for Atherosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang, 421001,China.
⁴ Department of Pathology, Huizhou Third People's Hospital, Guangzhou Medical University, Huizhou City, Guangdong Province 516001, China. Electronic address: xiaolong880101@126.com.

PMID: 32445748
DOI: 10.1016/j.yexcr.2020.112108

Abstract

Fibroblast growth factor 21(FGF21) is an endocrine cytokine that targets inflammation and atherosclerosis (AS). However, the underlying molecular mechanisms of the FGF21 anti-AS effect remain to be explored. Pyroptosis induced by hyperlipidemia or oxidized low-density lipoprotein (oxLDL) in vascular endothelial cells (VECs) is a significant step in the advancement of AS. This work aimed to evaluate the mechanisms and functioning of FGF21 against AS using an atherosclerotic animal model and oxLDL mimic in vitro. We found that exogenous treatments with FGF21 significantly reduced the aortic sinus plaque area and ameliorated dyslipidemia in apoE^-/- mice. FGF21 attenuated the expression of pyroptosis-related proteins both in vivo and in vitro. Possibly, FGF21 improves mitochondrial function, inhibits mitochondrial division, and reduces ROS production by maintaining mitochondrial dynamics and function to reduce NLRP3 related pyroptosis and inhibits VECs endoplasmic reticulum stress, thereby exerting an anti-atherosclerotic effect.

Keywords: Atherosclerosis; FGF21; Inflammasome; Pyroptosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Endoplasmic Reticulum Stress / drug effects
Endothelial Cells / drug effects*
Endothelial Cells / metabolism
Fibroblast Growth Factors / pharmacology*
Humans
Inflammasomes / drug effects*
Inflammasomes / metabolism
Male
Mitochondria / drug effects
Mitochondria / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein / drug effects
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Pyroptosis / drug effects*
Reactive Oxygen Species / metabolism

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3 protein, human
Nlrp3 protein, mouse
Reactive Oxygen Species
fibroblast growth factor 21
Fibroblast Growth Factors