Endothelial Progenitor Cells: Relevant Players in the Vasculopathy and Lung Fibrosis Associated with the Presence of Interstitial Lung Disease in Systemic Sclerosis Patients.

Verónica Pulito-Cueto,Alfonso Corrales,Raquel Pérez-Fernández,Belén Atienza-Mateo,Sara Remuzgo-Martínez,Miguel A González-Gay,Leticia Lera-Gómez,Fernanda Genre,David Iturbe-Fernández,Víctor M Mora-Cuesta,Diana Prieto-Peña,Raquel López-Mejías,Virginia Portilla,Oreste Gualillo,Ricardo Blanco,José M Cifrián

doi:10.3390/biomedicines9070847

Abstract

Endothelial progenitor cells (EPC), which are key effectors in the physiologic vascular network, have been described as relevant players in autoimmune diseases. We previously showed that EPC frequency may help to identify the presence of interstitial lung disease (ILD) in rheumatoid arthritis patients. Given that ILD constitutes the main cause of mortality in systemic sclerosis (SSc) patients, we aimed to determine the EPC contribution to the pathogenic processes of vasculopathy and lung fibrosis in SSc-ILD+. EPC quantification was performed by flow cytometry on blood from 83 individuals: 21 SSc-ILD+ patients and subjects from comparative groups (20 SSc-ILD− and 21 idiopathic pulmonary fibrosis (IPF) patients and 21 healthy controls (HC)). EPC were considered as CD34+, CD45low, CD309+, and CD133+. A significant increase in EPC frequency was found in SSc-ILD+ patients when compared to HC (p < 0.001). SSc-ILD+ patients exhibited a higher EPC frequency than SSc-ILD− patients (p = 0.012), whereas it was markedly reduced compared to IPF patients (p < 0.001). EPC frequency was higher in males (p = 0.04) and negatively correlated to SSc duration (p = 0.04) in SSc-ILD+ patients. Our results indicate a role of EPC in the processes of vasculopathy and lung fibrosis in SSc-ILD+. EPC frequency may be considered as a biomarker of ILD in SSc patients.

Highlights

Endothelial progenitor cells (EPC) frequency was increased in systemic sclerosis (SSc)-interstitial lung disease (ILD)+ patients compared to patients with SSc-ILD− (p = 0.012), whereas it was markedly reduced compared to IPF patients (p < 0.001) (Figure 1 and Table S1)
Given that we recently identified EPC as a potential biomarker of endothelial damage in rheumatoid arthritis (RA)-ILD+ [7], and based on the relevance of ILD as a main cause of mortality in patients with SSc [8,9,10,11,12], we wondered if EPC may play a crucial role in SSc-ILD+
We assessed the contribution of EPC to the pathogenic processes of vasculopathy and lung fibrosis in SSc-ILD+

Summary

Introduction

The investigation of novel, reliable, and non-invasive biomarkers would provide a better understanding of the pathophysiology of SSc-ILD [10,12]. In this context, EPC have been described as important players in the pathogenesis of SSc [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30]. To the best of our knowledge, their role in the development of ILD in SSc patients remains unknown

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Conclusion