| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Eur J Cardiothorac Surg 2007;32:35-41. doi:10.1016/j.ejcts.2007.04.006
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved
a Laboratory for Cardiovascular Research, Center for Anatomy and Cell Biology, Medical University of Vienna, Waehringerstr. 13, A-1090 Vienna, Austria
b Department of Cardiothoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Received 2 September 2006; received in revised form 29 March 2007; accepted 3 April 2007.
* Corresponding author. Address: Department of Cardiothoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Tel.: +43 140400 5620; fax: +43 140400 5640. (Email: seyedhossein.aharinejad{at}meduniwien.ac.at).
Objective: Vascular endothelial growth factor (VEGF) is the prime regulator of angiogenesis and vascular permeability and its serum levels increase in cystic fibrosis (CF). The mechanisms of VEGF overproduction and its impact on CF lung pathology and pulmonary vascular permeability during lung transplantation are not fully understood. Methods
: The expression of VEGF, its receptors, hypoxia inducible factor (HIF)-1
, ß, angiopoietins, and endothelial cell marker CD31 were studied in lung biopsies of CF and COPD patients and controls, using real time reverse transcription (RT)-PCR and Western blotting. DNA binding activity of HIF-1 to VEGF-A promoter was assessed by electrophoretic mobility shift assay (EMSA) and wet-to-dry lung weight ratios as well as microvascular density (MVD) were determined. Serum VEGF-A concentrations in enzyme-linked immunosorbent assay (ELISA) and wet-to-dry weight ratios of donor lungs were monitored during transplantation in CF and COPD patients. Primary graft dysfunction (PGD) was diagnosed and graded according to the guidelines of the International Society for Heart and Lung Transplantation. Results
: VEGF-A165 and Flt-1 mRNA expression (P
< 0.05), VEGF-A (P
< 0.05), and HIF-1 (P
< 0.05) protein levels, DNA binding activity of HIF-1 to VEGF promoter (P
< 0.001) and extravascular lung water content (P
< 0.05) were increased in CF lungs versus controls, whereas MVD was unchanged. Before and during lung transplantation, VEGF-A serum concentrations were higher in CF versus COPD patients (P
< 0.05) and 60 min following reperfusion donor lungs transplanted to CF patients had higher tissue water contents than in COPD patients (P
< 0.05). PGD grade 3 occurred more frequently in CF (22.7%) versus COPD patients (4%). PGD grade 3 patients had significantly higher VEGF serum concentrations versus PGD grade 0–2 patients (P
< 0.001). Conclusions
: These data indicate that upregulated VEGF-A levels are most likely induced by enhanced HIF-1 binding to VEGF-A promoter, possibly contributing to elevated serum VEGF-A levels in CF. Furthermore, CF patients undergoing lung transplantation are possibly more susceptible to PGD because of increased VEGF-A expression that mediates increased lung graft vascular permeability.
Key Words: Lung transplantation • Cystic fibrosis • VEGF • HIF • Vascular permeability
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
