The potential role of plasma fibroblast growth factor 21 as a diagnostic biomarker for abdominal aortic aneurysm presence and development

Life Sci. 2021 Jun 1:274:119346. doi: 10.1016/j.lfs.2021.119346. Epub 2021 Mar 10.

Abstract

Aims: 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.

Materials and methods: 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.

Key findings: 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.

Significance: 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.

Keywords: Abdominal aortic aneurysm; FGF21 resistance; Fibroblast growth factor 21; Machine learning; β-Klotho.

MeSH terms

  • Aged
  • Aortic Aneurysm, Abdominal / blood
  • Aortic Aneurysm, Abdominal / diagnosis*
  • Aortic Aneurysm, Abdominal / pathology
  • Biomarkers / blood*
  • Case-Control Studies
  • Female
  • Fibroblast Growth Factors / blood*
  • Fibroblast Growth Factors / genetics
  • Humans
  • Klotho Proteins
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Prognosis

Substances

  • Biomarkers
  • FGF21 protein, human
  • KLB protein, human
  • Membrane Proteins
  • Fibroblast Growth Factors
  • Klotho Proteins