D M Smadja1, H Nunes2, K Juvin3, S Bertil4, D Valeyre2, P Gaussem5, D Israel-Biet6. 1. Faculté de pharmacie, université Paris Descartes, Sorbonne Paris Cité, 4, avenue de l'Observatoire, 75006 Paris, France; Inserm UMR-S1140, faculté de pharmacie, 4, avenue de l'Observatoire, 75006 Paris, France; Service d'hématologie biologique, AP-HP, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France. Electronic address: David.smadja@egp.aphp.fr. 2. Service de pneumologie, AP-HP, hôpital Avicenne, EA2363, université Paris 13, 125, rue de Stalingrad, 93000 Bobigny, France. 3. Service de pneumologie, AP-HP, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France. 4. Service d'hématologie biologique, AP-HP, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France. 5. Faculté de pharmacie, université Paris Descartes, Sorbonne Paris Cité, 4, avenue de l'Observatoire, 75006 Paris, France; Inserm UMR-S1140, faculté de pharmacie, 4, avenue de l'Observatoire, 75006 Paris, France; Service d'hématologie biologique, AP-HP, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France. 6. Faculté de pharmacie, université Paris Descartes, Sorbonne Paris Cité, 4, avenue de l'Observatoire, 75006 Paris, France; Inserm UMR-S1140, faculté de pharmacie, 4, avenue de l'Observatoire, 75006 Paris, France; Service de pneumologie, AP-HP, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France.
Abstract
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with a marked pulmonary vascular remodeling. The aim of this study was to investigate a potential imbalance between angiogenic and angiostatic factors in this disease. METHODS AND RESULTS: Sixty-four subjects with IPF and 10 healthy control subjects (60-70 years old) were prospectively included in this multicenter study. Plasma levels of vascular endothelial growth factor A (VEGF-A), thrombospondin-1 (TSP-1) and stem cell factor (SCF) were determined by Elisa. Comparisons between IPF and controls were made using the Mann-Whitney U test. We also analyzed these soluble mediators in relation with IPF severity (DLCO<40% or>40%) predicted or total lung capacity (TLC) and forced vital capacity (FVC) (both<55% or>55% predicted) using the same test. VEGF-A plasma levels were increased in IPF vs. controls (P=0.0008) as well as those of TSP-1 (P=0.008), irrespective of the severity of the disease as reflected by DLCO, TLC or FVC values. In contrast, SCF levels were similar in IPF and controls. CONCLUSIONS: Factors modulating angiogenic responses are dysregulated in patients with IPF with increases in VEGF-A and TSP-1. The serial assessment of VEGF-A and TSP-1 during the follow-up and the search for potential relationships with the outcome of the disease might give us hints to the clinical implication of these results.
BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is associated with a marked pulmonary vascular remodeling. The aim of this study was to investigate a potential imbalance between angiogenic and angiostatic factors in this disease. METHODS AND RESULTS: Sixty-four subjects with IPF and 10 healthy control subjects (60-70 years old) were prospectively included in this multicenter study. Plasma levels of vascular endothelial growth factor A (VEGF-A), thrombospondin-1 (TSP-1) and stem cell factor (SCF) were determined by Elisa. Comparisons between IPF and controls were made using the Mann-Whitney U test. We also analyzed these soluble mediators in relation with IPF severity (DLCO<40% or>40%) predicted or total lung capacity (TLC) and forced vital capacity (FVC) (both<55% or>55% predicted) using the same test. VEGF-A plasma levels were increased in IPF vs. controls (P=0.0008) as well as those of TSP-1 (P=0.008), irrespective of the severity of the disease as reflected by DLCO, TLC or FVC values. In contrast, SCF levels were similar in IPF and controls. CONCLUSIONS: Factors modulating angiogenic responses are dysregulated in patients with IPF with increases in VEGF-A and TSP-1. The serial assessment of VEGF-A and TSP-1 during the follow-up and the search for potential relationships with the outcome of the disease might give us hints to the clinical implication of these results.
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