Abstract
Increased permeability and interstitial and pulmonary edema are prominent features of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) [1]. Vascular endothelial growth factor (VEGF) and its receptors have been implicated in the regulation of vascular permeability in many organ systems, including the lung. Data extrapolated from other organs and animal experiments have suggested that over-expression of VEGF would, therefore, be harmful within the lung. Recent data, from animal models as well as from patients with ALI, have shown decreased levels of VEGF in the lung. It is clear that the regulation of pulmonary vascular permeability and the roles of VEGF expression in the lung are complex. In this chapter, we explore the literature looking at the expression and function of VEGF in animal models of ALI and in patients with ALI. Novel evidence points to a potential role of VEGF in promoting repair of the alveolar-capillary membrane during recovery from ALI. Pro-VEGF therapy may therefore have potential as a rescue therapy for alveolar epithelial damage in ALI.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ware LB, Matthay MA (2000) The acute respiratory distress syndrome. N Engl J Med 342: 1334–1349
Lee YC (2005) The involvement of VEGF in endothelial permeability: a target for anti-inflammatory therapy. Curr Opin Investig Drugs 6: 1124–1130
Holmes DI, Zachary I (2005) The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease. Genome BioI 6: 209
Ladomery MR, Harper SJ, Bates DO (2007) Alternative splicing in angiogenesis: the vascular endothelial growth factor paradigm. Cancer Lett 249: 133–142
Medford ARL, Ibrahim NBN, Millar AB (2009) Vascular endothelial growth factor receptor and coreceptor expression in human acute respiratory distress syndrome. J Crit Care 24: 236–242
Thickett DR, Armstrong L, Millar AB (2002) A role for vascular endothelial growth factor in acute and resolving lung injury. Am J Respir Crit Care Med 166: 1332–1337
Boussat S, Eddahibi S, Coste A, et al (2000) Expression and regulation of vascular endothelial growth factor in human pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol 279: L371–378
Kaner RJ, Ladetto JV, Singh R, Fukuda N, Matthay MA, Crystal RG (2000) Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema. Am J Respir Cell Mol BioI 22: 657–664
Le Cras TD, Spitzmiller RE, Albertine KH, Greenberg JM, Whitsett JA, Akeson AL (2004) VEGF causes pulmonary hemorrhage) hemosiderosis) and air space enlargement in neonatal mice. Am J Physiol Lung Cell Mol Physiol 287: L134–142
Karmpaliotis D, Kosmidou I, Ingenito EP, et al (2002) Angiogenic growth factors in the pathophysiology of a murine model of acute lung injury. Am J Physiol Lung Cell Mol Physiol 283: L585–595
Maniscalco WM, Watkins RH, Finkelstein IN, Campbell MH (1995) Vascular endothelial growth factor mRNA increases in alveolar epithelial cells during recovery from oxygen injury. Am J Respir Cell Mol BioI 13: 377–386
Corne J, Chupp G, Lee CG, et al (2000) IL-13 stimulates vascular endothelial cell growth factor and protects against hyperoxic acute lung injury. J Clin Invest 106: 783–791
Kasahara Y, Tuder RM, Taraseviciene-Stewart L, et al (2000) Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest 106: 1311–1319
Compernolle V, Brusselmans K, Acker T, et al (2002) Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation) whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med 8: 702–710
Kaner RJ, Crystal RG (2001) Compartmentalization of vascular endothelial growth factor to the epithelial surface of the human lung. Mol Med 7: 240–246
Thickett DR, Armstrong L, Christie SJ, Millar AB (2001) Vascular endothelial growth factor may contribute to increased vascular permeability in acute respiratory distress syndrome. Am J Respir Crit Care Med 164: 1601–1605
Maitre B, Boussat S, Jean D, et al (2001) Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury. Eur Respir J 18: 100–106
Koh H, Tasaka S, Hasegawa N, et al (2008) Vascular endothelial growth factor in epithelial lining fluid of patients with acute respiratory distress syndrome. Respirology 13: 281–284
Perkins GD, Gao F, Thickett DR (2008) In vivo and in vitro effects of salbutamol on alveolar epithelial repair in acute lung injury. Thorax 63: 215–220
Ware LB, Kaner RJ, Crystal RG, et al (2005) VEGF levels in the alveolar compartment do not distinguish between ARDS and hydrostatic pulmonary oedema. Eur Respir J 26: 101–105
van der Flier M, van Leeuwen HJ, van Kessel KP, Kimpen JL, Hoepelman AI, Geelen SP (2005) Plasma vascular endothelial growth factor in severe sepsis. Shock 23: 35–38
Abadie Y, Bregeon F, Papazian L, et al (2005) Decreased VEGF concentration in lung tissue and vascular injury during ARDS. Eur Respir J 25: 139–146
Medford A, Douglas S, Godinho S, et al (2009) Vascular endothelial growth factor (VEGF) isoform expression and activity in human and murine lung injury. Respir Res 10: 27
Perkins GD, Nathani N, Richter AG, et al (2009) Type XVIII collagen degradation products in acute lung injury. Crit Care 13: R52
Perkins GD, Roberts J, McAuley DF, et al (2005) Regulation of vascular endothelial growth factor bioactivity in patients with acute lung injury. Thorax 60: 153–158
Mura M, dos Santos CC, Stewart D, Liu M (2004) Vascular endothelial growth factor and related molecules in acute lung injury. J Appl Physiol 97: 1605–1617
Voelkel NF, Vandivier RW, Tuder RM (2006) Vascular endothelial growth factor in the lung. Am J Physiol Lung Cell Mol Physiol 290: L209–221
Smith SF, Roberts NA, Guz A, Tetley TD (1996) Compromised inhibition of human lung lavage cell elastases. FEBS Lett 390: 187–190
Farkas L, Farkas D, Ask K, et al (2009) VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats. J Clin Invest 119: 1298–1311
Roberts JR, Perkins GD, Fujisawa T, et al (2007) Vascular endothelial growth factor promotes physical wound repair and is anti-apoptotic in primary distal lung epithelial and A549 cells. Crit Care Med 35: 2164–2170
Raoul W, Chailley-Heu B, Barlier-Mur AM, Delacourt C, Maitre B, Bourbon JR (2004) Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells. Am J Physiol Lung Cell Mol Physiol 286: L1293–1301
Barleon B, Sozzani S, Zhou D, Weich HA, Mantovani A, Marme D (1996) Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87: 3336–3343
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science + Business Media Inc.
About this paper
Cite this paper
D’Souza, V., Dancer, R.C.A., Thickett, D.R. (2010). Vascular Endothelial Growth Factor in Acute Lung Injury. In: Vincent, JL. (eds) Intensive Care Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5562-3_12
Download citation
DOI: https://doi.org/10.1007/978-1-4419-5562-3_12
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-5561-6
Online ISBN: 978-1-4419-5562-3
eBook Packages: MedicineMedicine (R0)