Abnormal Levels of Circulating Endothelial Progenitor Cells During Exacerbations of COPD

Abstract

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]; FEV(1) = 46 +/- 15% predicted), patients with stable COPD (n = 44; 68 +/- 8 years; FEV(1) = 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.

Pulmonary vascular changes in asthma and COPD

“…The potent pro-angiogenic factor VEGF is a known chemo-attractant of EPCs. Levels of VEGF-A have been correlated to the number of CD34+ cells (progenitor cell marker) in the plasma of COPD patients [62]. The increased presence and persistence of circulating EPCs in patients with asthma and COPD could be significant to the increased vasculature seen in these remodelled airways.…”

Impaired Colony-Forming Capacity of Circulating Endothelial Progenitor Cells in Patients with Emphysema

“…By contrast, Sala et al (2010) reported a positive relationship between plasma VEGF levels and the percentage of circulating EPCs (r = 0.51, p = 0.003) during COPD exacerbations. However, this correlation was not seen in stable COPD patients (r = 0.20, p = 0.22) (Sala et al 2010).…”

“…In patients with rheumatoid arthritis, VEGF and basic fibroblast growth factor levels do not correlate with EPC numbers (Grisar et al 2005). By contrast, Sala et al (2010) reported a positive relationship between plasma VEGF levels and the percentage of circulating EPCs (r = 0.51, p = 0.003) during COPD exacerbations. However, this correlation was not seen in stable COPD patients (r = 0.20, p = 0.22) (Sala et al 2010).…”

Endothelial progenitor cells in chronic obstructive pulmonary disease

“…However, as the authors only used markers of HSCs and did not use any specific endothelial marker such as kinase-insert domain receptor (KDR), they could not infer whether EPCs along with HSCs were reduced in COPD patients. In the same year, a cross-sectional study by Fadi 30 . The results showed that the levels of EPC were higher in ECOPD (n = 35) than patients with stable COPD (n = 44) and healthy controls (n = 20).…”

“…In COPD, few studies to date have investigated the number of circulating progenitor cells [22][23][24][28][29][30][31] . While most of the studies indicate lower levels of EPCs in COPD patients compared with controls [22][23][24]31 , others do not find a significant difference 28,30 .…”