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

Lia Pulsatelli, Luigi Boiardi, Elisa Assirelli, Giulia Pazzola, Francesco Muratore, Olga Addimanda, Paolo Dolzani, Annibale Versari, Massimiliano Casali, Barbara Bottazzi, Luca Magnani, Elettra Pignotti, Nicolò Pipitone, Stefania Croci, Alberto Mantovani, Carlo Salvarani, Riccardo Meliconi

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalClinical and Experimental Rheumatology
Publication statusE-pub ahead of print - Sep 17 2019

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Angiogenesis Inducing Agents
Vasculitis
Takayasu Arteritis
Angiostatins
Giant Cell Arteritis
Vascular Endothelial Growth Factor A
Serum
Endostatins
Positron-Emission Tomography
Enzyme-Linked Immunosorbent Assay
Angiopoietin-2
Angiopoietin-1
Vascular Cell Adhesion Molecule-1
Fluorodeoxyglucose F18
Fibroblast Growth Factor 2
Cluster Analysis
Research Design
Age Groups
PTX3 protein

Cite this

@article{713b72af463141018962f552a5d0aee1,
title = "Imbalance between angiogenic and anti-angiogenic factors in sera from patients with large-vessel vasculitis",
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.",
author = "Lia Pulsatelli and Luigi Boiardi and Elisa Assirelli and Giulia Pazzola and Francesco Muratore and Olga Addimanda and Paolo Dolzani and Annibale Versari and Massimiliano Casali and Barbara Bottazzi and Luca Magnani and Elettra Pignotti and Nicol{\`o} Pipitone and Stefania Croci and Alberto Mantovani and Carlo Salvarani and Riccardo Meliconi",
year = "2019",
month = "9",
day = "17",
language = "English",
journal = "Clinical and Experimental Rheumatology",
issn = "0392-856X",
publisher = "Clinical and Experimental Rheumatology S.A.S.",

}

TY - JOUR

T1 - Imbalance between angiogenic and anti-angiogenic factors in sera from patients with large-vessel vasculitis

AU - Pulsatelli, Lia

AU - Boiardi, Luigi

AU - Assirelli, Elisa

AU - Pazzola, Giulia

AU - Muratore, Francesco

AU - Addimanda, Olga

AU - Dolzani, Paolo

AU - Versari, Annibale

AU - Casali, Massimiliano

AU - Bottazzi, Barbara

AU - Magnani, Luca

AU - Pignotti, Elettra

AU - Pipitone, Nicolò

AU - Croci, Stefania

AU - Mantovani, Alberto

AU - Salvarani, Carlo

AU - Meliconi, Riccardo

PY - 2019/9/17

Y1 - 2019/9/17

N2 - 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.

AB - 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.

UR - https://www.ncbi.nlm.nih.gov/pubmed/31573481

M3 - Article

C2 - 31573481

JO - Clinical and Experimental Rheumatology

JF - Clinical and Experimental Rheumatology

SN - 0392-856X

ER -