Identification of vascular progenitor cells in pulmonary arteries of patients with chronic obstructive pulmonary disease.

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 undetermined. In this study we sought 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 nine patients with COPD and six control subjects were studied. Scanning electron microscopy demonstrated areas of denuded endothelium in the arteries of patients with COPD. 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 patients with COPD than in control subjects. 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 and with VEGF and VEGF receptor-2 mRNA expression. We conclude that patients with COPD 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.