Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema.

Margaret F Doyle,Steven Kawut,Megha A Parikh,R Graham Barr,Karol Watson,Daichi Shimbo,Antoinette Gomes,Jens Vogel-Claussen,Joao Lima,Russell P Tracy,Katja Hueper,John H M Austin,Benjamin M Smith,Eric A Hoffman,Jeffrey Chalmers

doi:10.1371/journal.pone.0173446

Abstract

Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema.

Highlights

Chronic obstructive pulmonary disease (COPD), the third leading cause of death in the US [1], is defined by airflow limitation that is not fully reversible[2], and is comprised of either chronic bronchitis, emphysema or both
endothelial progenitor cells (EPCs) populations were reduced in COPD, with CD34+KDR+ EPCs in particular being lower in both moderate and severe COPD compared to controls
CD34+KDR+CD133+ EPCs were preferentially lower with greater emphysema on CT and both EPC populations were lower with greater panlobular emphysema and reduced diffusing capacity

Summary

Introduction

Chronic obstructive pulmonary disease (COPD), the third leading cause of death in the US [1], is defined by airflow limitation that is not fully reversible[2], and is comprised of either chronic bronchitis, emphysema or both. No studies have reported on circulating levels of CECs in COPD, of which we are aware, but increased CECs have been observed in diseases of the vascular circulation [11,12,13,14,15,16,17,18]. This process causes the release of a variety of angiogenic factors, most notably, vascular endothelial growth factor (VEGF), which recruits endothelial progenitor cells (EPCs) to the site, presumably to repair the vascular damage [11,19]

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Conclusion