Published ahead of print on October 20, 2005, doi:10.1165/rcmb.2005-0255OC
Am. J. Respir. Cell Mol. Biol., Volume 34, Number 3, March 2006, 257-263
A more recent version of this article appeared on March 1, 2006
Submitted on July 11, 2005
Revised on October 20, 2005
Identification of Vascular Progenitor Cells in Pulmonary Arteries of Patients with COPD
Victor I Peinado1, Josep Ramirez2, Josep Roca1, Robert Rodriguez-Roisin1, and Joan A Barbera1*
1 Department of Pulmonary Medicine, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain,
2 Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
* To whom correspondence should be addressed. E-mail: jbarbera{at}clinic.ub.es.
Progenitor cells of bone marrow origin migrate to injured vessels, where they may contribute to endothelial maintenance and vessel remodeling, through vascular endothelial growth factor (VEGF) related signals. To what extent progenitor cells may play a role in vascular changes occurring in patients with chronic obstructive pulmonary disease (COPD) remains unsettled. The study was addressed to identify vascular progenitor cells in pulmonary arteries of patients with COPD and to investigate whether the presence of these cells could be related to changes in endothelial function or the expression of VEGF. Pulmonary arteries of 9 patients with COPD and 6 controls were studied. Scanning electron microscopy demonstrated areas of denuded endothelium in arteries of COPD patients. Vascular progenitor cells were identified by immunohistochemistry and immunogold using antibodies against AC133, CD34 and CD45. AC133+ cells were localized in the endothelial surface, close to denuded areas. The number of AC133+ and CD45+ cells in pulmonary arteries was greater in COPD patients than in controls. The number of AC133+ cells correlated with the response of pulmonary artery rings to hypoxic stimulus. AC133+ and CD45+ cells were also identified in the intimal layer. The wall thickness correlated with the number of progenitor cells in the intima, as well as with VEGF and VEGF receptor-2 mRNA expression. We conclude that COPD patients show an increased number of bone marrow-derived progenitor cells in pulmonary arteries. These cells seem to contribute to ongoing endothelial repair, but they might also be involved in the pathogenesis of pulmonary vascular remodeling.
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