School of Medical Sciences, UNSW Australia, Sydney, NSW, Australia.
School of Medical Sciences, UNSW Australia, Sydney, NSW, Australia.
Atherosclerosis. 2017 Feb;257:259-265. doi: 10.1016/j.atherosclerosis.2016.11.033. Epub 2016 Dec 1.
The metabolic properties of the endocrine fibroblast growth factor 21 (FGF21) have been extensively studied in the past decade. Previous studies have demonstrated the lipid-lowering, anti-inflammatory and anti-oxidant properties of FGF21. FGF21 is mainly secreted in the liver and adipose tissue in response to a range of physiological and pathological stimuli. In animal and in vitro studies, FGF21 has been shown to improve lipid profiles and inhibit key processes in the pathogenesis of atherosclerosis. It exerts its effects on the cardiovascular system via adiponectin dependent and independent mechanisms. However, the signalling pathways by which FGF21 exerts its effects on endothelial cells remains unknown and needs to be further investigated. The elevation of circulating FGF21 levels in cardiovascular disease has also raised questions as to whether FGF21 can be used as a biomarker to predict subclinical atherosclerosis and cardiovascular events. Recent findings from population studies must be validated in independent cohorts before FGF21 can be used as a biomarker in the clinical setting. The anti-atherosclerotic effects of FGF21 have been investigated in two recent clinical trials, where treatment with an FGF21 analog significantly improved the cardiometabolic profile in obese patients with type 2 diabetes. This review will evaluate recent advances that suggest there may be a role for FGF21 in atherosclerosis.
在过去的十年中，人们对内分泌成纤维细胞生长因子 21（FGF21）的代谢特性进行了广泛的研究。先前的研究表明，FGF21 具有降低血脂、抗炎和抗氧化的特性。FGF21 主要在肝脏和脂肪组织中分泌，以响应一系列生理和病理刺激。在动物和体外研究中，FGF21 已被证明可以改善脂质谱并抑制动脉粥样硬化发病机制中的关键过程。它通过脂联素依赖和非依赖机制对心血管系统发挥作用。然而，FGF21 对内皮细胞发挥作用的信号通路尚不清楚，需要进一步研究。心血管疾病中循环 FGF21 水平的升高也引发了一个问题，即 FGF21 是否可以用作预测亚临床动脉粥样硬化和心血管事件的生物标志物。在 FGF21 可用于临床之前，必须在独立队列中验证人群研究的最新发现。最近的两项临床试验研究了 FGF21 的抗动脉粥样硬化作用，其中使用 FGF21 类似物治疗可显著改善 2 型糖尿病肥胖患者的心脏代谢状况。这篇综述将评估最近的研究进展，这些进展表明 FGF21 可能在动脉粥样硬化中发挥作用。
