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.

中文翻译：

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FGF21通过抑制NLRP3炎性体介导的血管内皮细胞热解减轻动脉粥样硬化。

成纤维细胞生长因子21（FGF21）是靶向炎症和动脉粥样硬化（AS）的内分泌细胞因子。然而，FGF21抗AS作用的潜在分子机制仍有待探索。高脂血症或氧化型低密度脂蛋白（oxLDL）在血管内皮细胞（VEC）中诱导的细胞凋亡是AS进步的重要一步。这项工作旨在使用动脉粥样硬化动物模型和oxLDL模拟物评估FGF21对抗AS的机制和功能。我们发现，FGF21的外源治疗显着减少了apoE-/-小鼠的主动脉窦斑块面积并改善了血脂异常。FGF21在体内和体外均减弱了与凋亡相关蛋白的表达。FGF21可能会改善线粒体功能，抑制线粒体分裂，