title: Elevated vascular endothelial growth factor is correlated with elevated erythropoietin in stable, young cystic fibrosis patients.
abstract: Angiogenesis is an important mechanism of airway remodeling in lung disease. We previously demonstrated that serum vascular endothelial growth factor (VEGF) is elevated in cystic fibrosis (CF) patients and declines with therapy for pulmonary exacerbation. We hypothesized that VEGF is elevated early in the course of CF and is associated with markers of tissue hypoxia. A prospective, single-visit evaluation of thirty stable infants and children with CF was performed. Serum was analyzed for VEGF and for other markers of tissue hypoxia (erythropoietin (EPO), insulin-like growth factor binding protein-1 (IGFBP-1)) and for inflammatory mediators (IL-1 beta, IL-6, IL-8, and tumor necrosis factor alpha (TNFα)) using Meso Scale multi-spot serum immunoassays. Measurements were correlated between assay groups; and with age in months and pulmonary function (FEV0.5 or FEV1). VEGF, EPO, TNFα and IL-8 were elevated compared to published normative values. VEGF levels were not significantly correlated with any inflammatory mediators. However, VEGF correlated with EPO (r=0.505; P<0.05). There was no correlation between lung function and markers of inflammation or tissue hypoxia. VEGF is elevated in young, stable infants and children suggesting angiogenesis as a contributing mechanism for early lung disease in CF. VEGF elevation does not show significant correlation with inflammatory mediators known to be increased in CF, but is significantly correlated with EPO levels. We propose that VEGF elevation and angiogenesis contribute to early lung disease and may result from a direct tissue hypoxia pathway in CF.
authors.affiliation: The Division of Pulmonary Medicine, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614, USA. kwatts@childrensmemorial.org
authors.forename: Kimberly Danieli
authors.initials: KD
authors.lastname: Watts
authors.forename: Susanna A
authors.initials: SA
authors.lastname: McColley
mesh_terms: D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000097:blood*; D016207:Cytokines / Q000097:blood; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood; D008168:Lung / Q000503:physiopathology; D008297:Male; D009752:Nutritional Status; D011446:Prospective Studies; D012129:Respiratory Function Tests; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D016207:Cytokines; C554270:EPO protein, human; D018836:Inflammation Mediators; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin