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

1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17

  1. Laboratory of Immunorheumatology and Tissue Regeneration, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. lia.pulsatelli@ior.it
  2. Division of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy.
  3. Laboratory of Immunorheumatology and Tissue Regeneration, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
  4. Division of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy.
  5. Division of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy.
  6. Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, and Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.
  7. Laboratory of Immunorheumatology and Tissue Regeneration, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
  8. Nuclear Medicine Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy.
  9. Nuclear Medicine Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy.
  10. Department of Inflammation and Immunology, Humanitas Clinical and Research Center IRCCS, Milan, Italy.
  11. Division of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy.
  12. Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
  13. Division of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy.
  14. Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy.
  15. Department of Inflammation and Immunology, Humanitas Clinical and Research Center IRCCS, Milan; Humanitas University, Milan, Italy, and The William Harvey Research Institute, Queen Mary University of London, UK.
  16. Division of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, and University of Modena and Reggio Emilia, Italy.
  17. Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, and Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.

CER12023 Submission on line
Full Papers

Rheumatology Article
Rheumatology Article

 

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.

PMID: 31573481 [PubMed]

Received: 27/12/2018 - Accepted : 01/07/2019 - In Press: 17/09/2019