Imbalance between angiogenic and anti-angiogenic factors in sera from patients with large-vessel vasculitis

Clin Exp Rheumatol. 2020 Mar-Apr;38 Suppl 124(2):23-30. Epub 2019 Sep 17.

Abstract

Objectives: To investigate serum levels of a panel of angiogenic inducers (VEGF, FGF-2, Angiopoietin 1, -2, soluble VCAM-1) and inhibitors (angiostatin, endostatin, pentraxin-3) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK), in order to gain further insights into the molecular mechanisms driving angiogenesis dysregulation in large-vessel vasculitis (LVV).

Methods: Sera were obtained from 33 TAK patients and 14 GCA patients and from two groups of age-matched normal controls (NC). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Angiogenic and anti-angiogenic factor serum levels were evaluated using commercial ELISA kits. Pentraxin 3 (PTX3) serum levels were evaluated by non-commercial ELISA, as already described.

Results: Among the angiogenic factors, only VEGF serum levels were significantly higher in TAK patients compared to NC. No difference was found between angiogenic factor levels in GCA patients compared to those detected in NC. Anti-angiogenic factor (Angiostatin, Endostatin, PTX3) serum levels were significantly higher in both GCA and TAK patients compared to NC. Significant associations were observed between VEGF and PTX3 levels and disease activity evaluated using PET scan and clinical indices. Cluster analysis based on PET scan scores in TAK patients showed significant ordered differences in VEGF and angiostatin serum levels. Indeed, we noted a progressive increase of VEGF and angiostatin from NC to the cluster including patients with the highest and more diffuse scan positivity.

Conclusions: Our overall results demonstrate a circulating molecular profile characterised by a prevailing expression of anti-angiogenic soluble factors.

MeSH terms

  • Angiogenic Proteins / blood*
  • Angiopoietin-1
  • Angiopoietin-2
  • Angiostatic Proteins / blood*
  • Angiostatins
  • C-Reactive Protein
  • Endostatins
  • Fibroblast Growth Factor 2
  • Giant Cell Arteritis / blood*
  • Humans
  • Neovascularization, Pathologic / blood
  • Positron Emission Tomography Computed Tomography
  • Positron-Emission Tomography
  • Serum Amyloid P-Component
  • Takayasu Arteritis / blood*
  • Vascular Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A

Substances

  • ANGPT1 protein, human
  • ANGPT2 protein, human
  • Angiogenic Proteins
  • Angiopoietin-1
  • Angiopoietin-2
  • Angiostatic Proteins
  • Endostatins
  • Serum Amyloid P-Component
  • VEGFA protein, human
  • Vascular Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • PTX3 protein
  • Angiostatins
  • C-Reactive Protein