Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
Life Sci. 2021 Jun 1;274:119346. doi: 10.1016/j.lfs.2021.119346. Epub 2021 Mar 10.
Fibroblast growth factor 21 (FGF21) has been identified as the master hormonal regulator of energy balance, its elevation is observed in a series of metabolic and cardiovascular diseases. Studies have implicated the role of FGF21 signaling in the pathogenesis of abdominal aortic aneurysm (AAA). We will investigate the association of FGF21 and AAA development.
In this study, we assayed plasma levels of FGF21 in 82 patients with AAA and 44 control subjects, then analyzed their relationship with clinical, biochemical and histological phenotypes. The expression of β-klotho, an essential co-receptor of FGF21, was assessed with IHC staining and RT-qPCR. Machine learning models incorporate a combination of FGF21 and clinical data were utilized in the prediction of AAA occurrence.
FGF21 was statistically higher in patients with AAA (781 pg/ml [533, 1213]) than in control subjects (567 pg/ml [324, 939]). After adjustment for age and BMI, we found a positive association of FGF21 levels with AAA diameters, hypertension rate and hsCRP, and a negative correlation between FGF21 levels and HDL-c. Furthermore, the protein levels of β-klotho in abdominal aorta of AAA were found significantly lower than in control group indicating the presence of FGF21 resistance. Combining FGF21 levels with four clinical characteristics significantly improved the stratification of AAA and control groups with an AUC of 0.778.
Combining detection of plasma FGF21 and clinical characteristics may be reliable for identifying the presence of AAA. The role of FGF21 as a therapeutic target of AAA warrants further investigation.
成纤维细胞生长因子 21(FGF21)已被确定为能量平衡的主要激素调节剂,其在一系列代谢和心血管疾病中升高。研究表明 FGF21 信号在腹主动脉瘤(AAA)的发病机制中起作用。我们将研究 FGF21 与 AAA 发展之间的关系。
在这项研究中,我们检测了 82 例 AAA 患者和 44 例对照者的血浆 FGF21 水平,然后分析了它们与临床、生化和组织学表型的关系。用免疫组化染色和 RT-qPCR 评估 FGF21 的必需共受体β-klotho 的表达。将包含 FGF21 和临床数据的组合的机器学习模型用于 AAA 发生的预测。
AAA 患者的 FGF21 水平明显高于对照组(781pg/ml[533,1213]比 567pg/ml[324,939])。在调整年龄和 BMI 后,我们发现 FGF21 水平与 AAA 直径、高血压发生率和 hsCRP 呈正相关,与 HDL-c 呈负相关。此外,AAA 腹主动脉β-klotho 的蛋白水平明显低于对照组,表明存在 FGF21 抵抗。将 FGF21 水平与四个临床特征相结合,可显著提高 AAA 和对照组的分层,AUC 为 0.778。
联合检测血浆 FGF21 和临床特征可能是识别 AAA 存在的可靠方法。FGF21 作为 AAA 的治疗靶点的作用值得进一步研究。