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Estudio de la angiogénesis en la patología pleural y su asociación con los marcadores de actividad neutrofílica, el sistema de la fibrinolisis y la matriz extracelular

by Ruiz Ruiz, Eva

Abstract (Summary)
Introduction: Pleural effusion is a common clinical entity, though its pathophysiology is still uncertain. The angiogenesis system has been implicated in inflammatory and neoplastic processes; nevertheless, it has been little studied in relation to the pleural space. Aims: 1) To analyze pleural and plasma levels of the activator and inhibitor factors of angiogenesis in the various types of pleural effusion; 2) To estimate the association of these factors with related biochemical markers, leukocyte count, inflammatory markers, fibrinolysis system parameters and metalloproteinases; and 3) To study the association between the angiogenesis factors and the presence of complications in infectious pleural effusions. Patients and method: Samples from 21 patients with each of the following etiological types of pleural effusion were studied: empyema or complicated parapneumonic, non-complicated parapneumonic, tuberculous, neoplastic and transudative effusions. Plasma and pleural fluid related biochemical markers (glucose, proteins, ADA, LDH, pH), cellularity (leukocyte count and differential count), inflammatory markers (elastase, IL-8, TNF-alpha), fibrinolysis system (plasminogen activatorsPA, t-PAand inhibitorsPAI-1, PAI-2), metalloproteinase system (MMP-2, MMP-9 and their inhibitors, TIMP-1, TIMP-2) and angiogenesis system (activatorstotal and free vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (b-FGF)and inhibitorsendostatin and thrombospondin-1 (TSP-1). Statistical package: SPSS. Results: VEGF and b-FGF were higher in exudates than in transudates (p<0.001) and in complicated parapneumonic patients and empyema than in non-complicated parapneumonic patients (p<0.001). Endostatin showed no significant differences in the various effusion groups, except the parapneumonic, where levels were higher in the non-complicated than in the empyema and complicated parapneumonic patients (p=0.002). TSP-1 showed higher levels in the exudates than in the transudates and in complicated parapneumonic effusions and empyema than in non-complicated parapneumonic effusions (p<0.001). In pleural exudates there was a positive correlation of VEGF, b-FGF and TSP-1 with low glucose and pH and high LDH, IL-8, elastin and TNF-alfa. Furthermore, VEGF, b-FGF and TSP-1 showed a positive association with PAIs and MMP-9 and a negative association with t-PA and MMP-2 in pleural exudates. With the exception of TSP-1, the factors implicated in angiogenesis presented higher levels in pleural fluid than in plasma. Except for endostatin in parapneumonic PE, there was no correlation between pleural and plasma levels of the angiogenesis factors. Parapneumonic PE, which showed highest values of VEGF, b-FGF and TSP-1 presented a higher incidence of pachypleuritis. Conclusions: 1) Exudative pleural effusions showed higher VEGF, b-FGF and TSP-1 values than transudative effusions, with the empyema and complicated parapneumonic groups displaying the highest values. There was no correlation between pleural and plasma concentrations, suggesting a compartmentalized response at the pleural level. 2) Exudates showed a positive correlation of VEGF, b-FGF and TSP-1 with low glucose and pH, and high LDH, inflammation markers, PAIs and MMP-9, and a negative correlation with t-PA and MMP-2. 3) Bacterial parapneumonic effusions with higher levels of VEGF, b-FGF and TSP-1 presented a higher incidence of pachypleuritis and could be predictors of late-onset pleural complications. 4) This study provides new data on the role of angiogenesis in the pathophysiology of exudative pleural effusions and on the association between angiogenesis and inflammation, the fibrinolysis system and the extracellular matrix.
This document abstract is also available in Spanish.
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Bibliographical Information:

Advisor:Alegre Martín, José; Alemán Mansó, Carmen

School:Universitat Autónoma de Barcelona

School Location:Spain

Source Type:Master's Thesis

Keywords:417 departament de medicina

ISBN:

Date of Publication:06/26/2004

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