Endothelial progenitor cells in the pathogenesis of idiopathic pulmonary fibrosis: an evolving concept

PLoS One. 2013;8(1):e53658. doi: 10.1371/journal.pone.0053658. Epub 2013 Jan 14.

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) has been associated with abnormal vascular remodeling. Bone marrow derived endothelial progenitor cells (EPCs) are considered to possess lung tissue repair and vascular remodeling properties.

Objectives: The study aimed to assess early EPCs levels and EPCs endogenous vascular endothelial growth factor (VEGF) expression in IPF. In order to examine alterations in the mobilization of EPCs from the bone marrow we measured plasma VEGF.

Main results: Twenty-three patients with IPF and fifteen healthy subjects were included. The number of early EPCs colonies was markedly reduced in IPF patients vs controls (6.00±6.49 vs 49.68±16.73, respectively, p<0.001). EPCs were further decreased in patients presenting systolic pulmonary arterial pressure (sPAP)≥35 mmHg. The number of colonies per well correlated negatively with P((A-a))O(2) (r = -0.750, p<0.001). Additionally, VEGF mRNA levels were significantly increased in IPF patients. There were no differences observed in VEGF plasma levels in IPF patients when compared to controls.

Conclusions: The current data suggest that inadequate levels of early EPCs may potentially contribute to suppressed repair and recovery of the damaged pulmonary endothelium and thereby may drive the sequence of events in profibrogenic direction. Increased VEGFmRNA levels in the clinical context of IPF may represent a compensatory mechanism to overcome reduced EPCs levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bone Marrow Cells / pathology
  • Cell Culture Techniques
  • Endothelial Cells / pathology*
  • Gene Expression Regulation
  • Humans
  • Idiopathic Pulmonary Fibrosis / etiology*
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / pathology*
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Male
  • Neovascularization, Pathologic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Solubility
  • Stem Cells / pathology*
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor A / chemistry
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • RNA, Messenger
  • Vascular Endothelial Growth Factor A

Grant support

This work was supported by a grant from the Hellenic Thoracic Society to FM and ZD. The funders of the study had no role in study design, data collection, data analysis, decision to publish, data interpretation, or the preparation of the manuscript.