Longitudinal Measurement of Serum Vascular Endothelial Growth Factor in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Background: Impaired vascular endothelial growth factor (VEGF) signaling causes emphysema in animal models. In chronic obstructive pulmonary disease (COPD) patients, alterations in VEGF tissue expression have been observed. We hypothesize that circulating VEGF may be a biomarker to phenotype COPD patients. Objective: The aim of this study was to investigate VEGF serum levels in stable and exacerbated COPD. Methods: VEGF serum levels as well as parameters of short- and long-term outcome were assessed and analyzed in two COPD cohorts [PROMISE, n = 117; ProCOLD (PC), n = 191]. Results: VEGF serum levels at stable COPD were neither related to forced expiratory volume in 1 s nor to the Modified Medical Research Council dyspnea score, 6-min walking distance or BODE index. There was no association between single VEGF levels and COPD exacerbation frequency or mortality at 1 and 2 years of follow-up. In PC an increase in VEGF over time (ΔVEGF) was associated with the exacerbation frequency as well as the 1- and 2-year hospitalization rate (p = 0.046, 0.009 and 0.006, respectively). Furthermore, in PC ΔVEGF was associated with 1- and 2-year survival (p = 0.009 and 0.041, respectively). Conclusions: Single serum VEGF levels, at stable and exacerbated COPD, were not associated with clinically significant outcomes in COPD. Conversely, the VEGF course seems related to COPD prognosis.

IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes

“…This is in line with what is known for hepatitis and diabetes, where the SNP rs8099917 GG genotype is considered to be the risk genotype and the SNP rs12979860 CC genotype the protective genotype [35][36][37]. The IFNL3 polymorphisms predict response to treatment in patients with hepatitis C [27,30,31]. We found that the prevalence of malignancy was increased among patients with the rs8099917 GG genotype.…”

“…1). Details of inclusion and exclusion criteria were previously published [27]. We analysed data from 528 patients, who completed the first 6 month-follow-up of the study and for whom serum samples from visit 1 were available.…”

VEGF synthesis is induced by prostacyclin and TGF‐β in distal lung fibroblasts from COPD patients and control subjects: Implications for pulmonary vascular remodelling

“…COPD patients with chronic bronchitis had increased VEGF levels in sputum in contrast to COPD patients with emphysema who had decreased VEGF levels . Patients with acute exacerbations presented high levels of VEGF in the circulation compared with stable COPD patients and healthy subjects, and increasing circulating VEGF longitudinal course appears to be related to poorer COPD prognosis . In this study, all the VEGFR were expressed by the lung fibroblasts, and especially VEGFR3, which has not previously been shown.…”

Vasogenic cerebral edema associated with the disability in activities of daily living in patients with chronic obstructive pulmonary disease

“…Vascular endothelial growth factor (Boeck et al., 2015), free radicals (Rossman et al., 2013), matrix metalloproteinase‐9 (Vlahos et al., 2012), and systemic inflammation (Furutate et al., 2016) have been found to play a role in the modulation of BBB permeability after hypoxic stress in COPD. The vascular endothelial growth factor‐mediated increase in BBB permeability involves nitric oxide‐ and cGMP‐dependent pathways (Schoch et al., 2002).…”

“…Hypoxia can induce the release of vascular endothelial growth factor (Boeck et al., 2015), free radicals (Rossman et al., 2013), and proteolytic enzymes matrix metalloproteinase‐9 (Vlahos, Wark, Anderson, & Bozinovski, 2012). Systemic inflammation is also present in patients with COPD (Furutate et al., 2016).…”