Endostatin as a biomarker of systemic sclerosis: insights from a systematic review and meta-analysis

IntroductionThe critical role played by vascular dysfunction and ineffective angiogenesis in the pathophysiology of systemic sclerosis (SSc) suggests that circulating biomarkers reflecting these alterations may be useful in the clinical evaluation of this patient group. We sought to address this iss...

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Main Authors: Arduino A. Mangoni, Angelo Zinellu
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1450176/full
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author Arduino A. Mangoni
Arduino A. Mangoni
Angelo Zinellu
author_facet Arduino A. Mangoni
Arduino A. Mangoni
Angelo Zinellu
author_sort Arduino A. Mangoni
collection DOAJ
description IntroductionThe critical role played by vascular dysfunction and ineffective angiogenesis in the pathophysiology of systemic sclerosis (SSc) suggests that circulating biomarkers reflecting these alterations may be useful in the clinical evaluation of this patient group. We sought to address this issue by conducting a systematic review and meta-analysis of studies investigating a such candidate biomarker, endostatin, an endogenous glycoprotein exerting anti-angiogenic effects, in SSc patients and healthy controls.MethodsA literature search was conducted in the electronic databases Web of Science, PubMed, and Scopus from inception to 27 May 2024. Risk of bias and certainty of evidence were assessed using the JBI checklist for analytical studies and GRADE, respectively.ResultsIn 19 eligible studies, circulating endostatin concentrations were significantly higher in SSc patients than controls (standard mean difference, SMD=0.90, 95% CI 0.56 to 1.23, p<0.001; low certainty of evidence). Endostatin concentrations were also significantly higher in SSc patients with digital ulcers than those without (SMD=0.43, 95% CI 0.24 to 0.62, p<0.001; very low certainty of evidence) and in patients with pulmonary arterial hypertension than those without (SMD=1.21, 95% CI 0.67 to 1.76, p<0.001; very low certainty of evidence). By contrast, no significant differences were observed between SSc patients with limited vs. diffuse disease and those with different video capillaroscopy patterns. There was limited evidence regarding endostatin concentrations in SSc patients with interstitial lung disease, telangiectasias, and gastrointestinal manifestations. There were no significant associations in meta-regression and subgroup analysis of studies investigating endostatin in SSc patients and controls between the effect size and various patient and study characteristics.DiscussionTherefore, the results of this systematic review and meta-analysis suggest that measuring endostatin can be useful in assessing the presence of SSc and specific complications, i.e., digital ulcers and pulmonary arterial hypertension, in these patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024558174.
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spelling doaj-art-a331af9510b44d1bb34b71da94980f802025-08-20T01:57:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14501761450176Endostatin as a biomarker of systemic sclerosis: insights from a systematic review and meta-analysisArduino A. Mangoni0Arduino A. Mangoni1Angelo Zinellu2Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, SA, AustraliaDepartment of Clinical Pharmacology, Flinders Medical Centre, Southern Adelaide Local Health Network, Bedford Park, SA, AustraliaDepartment of Biomedical Sciences, University of Sassari, Sassari, ItalyIntroductionThe critical role played by vascular dysfunction and ineffective angiogenesis in the pathophysiology of systemic sclerosis (SSc) suggests that circulating biomarkers reflecting these alterations may be useful in the clinical evaluation of this patient group. We sought to address this issue by conducting a systematic review and meta-analysis of studies investigating a such candidate biomarker, endostatin, an endogenous glycoprotein exerting anti-angiogenic effects, in SSc patients and healthy controls.MethodsA literature search was conducted in the electronic databases Web of Science, PubMed, and Scopus from inception to 27 May 2024. Risk of bias and certainty of evidence were assessed using the JBI checklist for analytical studies and GRADE, respectively.ResultsIn 19 eligible studies, circulating endostatin concentrations were significantly higher in SSc patients than controls (standard mean difference, SMD=0.90, 95% CI 0.56 to 1.23, p<0.001; low certainty of evidence). Endostatin concentrations were also significantly higher in SSc patients with digital ulcers than those without (SMD=0.43, 95% CI 0.24 to 0.62, p<0.001; very low certainty of evidence) and in patients with pulmonary arterial hypertension than those without (SMD=1.21, 95% CI 0.67 to 1.76, p<0.001; very low certainty of evidence). By contrast, no significant differences were observed between SSc patients with limited vs. diffuse disease and those with different video capillaroscopy patterns. There was limited evidence regarding endostatin concentrations in SSc patients with interstitial lung disease, telangiectasias, and gastrointestinal manifestations. There were no significant associations in meta-regression and subgroup analysis of studies investigating endostatin in SSc patients and controls between the effect size and various patient and study characteristics.DiscussionTherefore, the results of this systematic review and meta-analysis suggest that measuring endostatin can be useful in assessing the presence of SSc and specific complications, i.e., digital ulcers and pulmonary arterial hypertension, in these patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024558174.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1450176/fullendostatinsystemic sclerosisbiomarkersvascular dysfunctionineffective angiogenesisfibrosis
spellingShingle Arduino A. Mangoni
Arduino A. Mangoni
Angelo Zinellu
Endostatin as a biomarker of systemic sclerosis: insights from a systematic review and meta-analysis
Frontiers in Immunology
endostatin
systemic sclerosis
biomarkers
vascular dysfunction
ineffective angiogenesis
fibrosis
title Endostatin as a biomarker of systemic sclerosis: insights from a systematic review and meta-analysis
title_full Endostatin as a biomarker of systemic sclerosis: insights from a systematic review and meta-analysis
title_fullStr Endostatin as a biomarker of systemic sclerosis: insights from a systematic review and meta-analysis
title_full_unstemmed Endostatin as a biomarker of systemic sclerosis: insights from a systematic review and meta-analysis
title_short Endostatin as a biomarker of systemic sclerosis: insights from a systematic review and meta-analysis
title_sort endostatin as a biomarker of systemic sclerosis insights from a systematic review and meta analysis
topic endostatin
systemic sclerosis
biomarkers
vascular dysfunction
ineffective angiogenesis
fibrosis
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1450176/full
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