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Published in: Angiogenesis 1/2013

01-01-2013 | Original Paper

Imbalance of circulating endothelial cells and progenitors in idiopathic pulmonary fibrosis

Authors: David M. Smadja, Laetitia Mauge, Hilario Nunes, Clément d’Audigier, Karine Juvin, Raphael Borie, Zohra Carton, Sébastien Bertil, Anne Blanchard, Bruno Crestani, Dominique Valeyre, Pascale Gaussem, Dominique Israel-Biet

Published in: Angiogenesis | Issue 1/2013

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Abstract

Background

Fibrogenesis during idiopathic pulmonary fibrosis (IPF) is strongly associated with abnormal vascular remodeling. Respective abundance of circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) might reflect the balance between vascular injury and repair and potentially serve as biomarkers of the disease.

Objectives and Methods

We postulated that CEC and EPC subtypes might be differently modulated in IPF. Sixty-four consecutive patients with newly diagnosed IPF were prospectively enrolled and compared to thirteen healthy volunteers. CEC were counted with immunomagnetic CD146-coated beads; progenitors CD34+45dim/CD34+133+/CD34+KDR+were assessed through flow cytometry and EPC (colony-forming-units-Endothelial Cells, CFU-EC, and endothelial colonies forming cells, ECFC) were quantified by cell culture assays.

Results

IPF patients were characterized by a marked increase in CEC associated to an EPC defect: both CD34+KDR+ cells and CFU-EC were decreased versus controls. Moreover, in IPF subjects with a low diffusing capacity of the lung for carbon monoxide (DLCO) < 40 %, CFU-EC and ECFC were higher compared to those with DLCO > 40 %. Finally, ECFC were negatively correlated with DLCO. During an 18 month follow up, CEC levels increased in patients with exacerbation, including those who died during follow up. Finally, ECFC from patients with exacerbation proliferative potential was strongly increased.

Conclusion

IPF is basically associated with both a vascular injury and a repair defect. This study highlights an adaptative process of EPC mobilization in the most severe forms of IPF, that could reflect enhanced homing to the pulmonary vasculature, which clinical consequences remain to be determined.
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Metadata
Title
Imbalance of circulating endothelial cells and progenitors in idiopathic pulmonary fibrosis
Authors
David M. Smadja
Laetitia Mauge
Hilario Nunes
Clément d’Audigier
Karine Juvin
Raphael Borie
Zohra Carton
Sébastien Bertil
Anne Blanchard
Bruno Crestani
Dominique Valeyre
Pascale Gaussem
Dominique Israel-Biet
Publication date
01-01-2013
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 1/2013
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-012-9306-9

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