Abnormal Levels of Circulating Endothelial Progenitor Cells During Exacerbations of COPD

Cardiovascular morbidity and mortality is increased in patients with chronic obstructive pulmonary disease (COPD). Reduced levels of circulating endothelial progenitor cells (EPCs) are associated with increased risk of death in patients with stable coronary artery disease (CAD). Likewise, during acute events of CAD, the number of circulating EPCs increases under the influence of vascular endothelial growth factor (VEGF) and systemic inflammation. Abnormal levels of circulating EPCs have been reported in patients with COPD. However, the response of EPCs to episodes of exacerbation of the disease (ECOPD) has not been investigated yet. We hypothesized that similar to what occurs during acute events of CAD, levels of circulating EPCs would increase during ECOPD. We compared levels of circulating EPCs (assessed by the % of CD34⁺KDR⁺ cells determined by flow cytometry) in patients hospitalized because of ECOPD (n = 35; 65 ± 9 years [mean ± SD]; FEV₁ = 46 ± 15% predicted), patients with stable COPD (n = 44; 68 ± 8 years; FEV₁ = 49 ± 17% predicted), smokers with normal lung function (n = 10; 60 ± 9 years), and healthy never smokers (n = 10; 62 ± 4 years). To investigate potential mechanisms of EPC regulation, we assessed both VEGF and high-sensitivity C-reactive protein (hsC-RP) in plasma. Our results show that EPC levels were higher (p < 0.05) in patients with ECOPD (1.46 ± 1.63%) than in those with stable disease (0.68 ± 0.83%), healthy smokers (0.65 ± 1.11%), and healthy never smokers (1.05 ± 1.36%). The percentage of circulating EPCs was positively related to VEGF plasma levels during ECOPD (r = 0.51, p = 0.003). In a subset of 12 patients who could be studied during both ECOPD and clinical stability, the EPCs levels increased during ECOPD. We conclude that EPC levels are increased during ECOPD, likely in relation to VEGF upregulation.