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Thorax. Feb 2005; 60(2): 153–158.
PMCID: PMC1747283

Regulation of vascular endothelial growth factor bioactivity in patients with acute lung injury

Abstract

Methods: Forty one patients with ARDS, 12 at risk of developing ARDS, and 16 normal controls were studied. Bioactive VEGF, total VEGF, and sVEGFR-1 were measured by ELISA in plasma and bronchoalveolar lavage (BAL) fluid. Reverse transcriptase polymerase chain reaction for sVEGFR-1 was performed on BAL cells.

Results: sVEGFR-1 was detectable in the BAL fluid of 48% (20/41) of patients with early ARDS (1.4–54.8 ng/ml epithelial lining fluid (ELF)) compared with 8% (1/12) at risk patients (p = 0.017) and none of the normal controls (p = 0.002). By day 4 sVEGFR-1 was detectable in only 2/18 ARDS patients (p = 0.008). Patients with detectable sVEGFR-1 had lower ELF median (IQR) levels of bioactive VEGF than those without detectable sVEGFR-1 (1415.2 (474.9–3192) pg/ml v 4761 (1349–7596.6) pg/ml, median difference 3346 pg/ml (95% CI 305.1 to 14711.9), p = 0.016), but there was no difference in total VEGF levels. BAL cells expressed mRNA for sVEGFR-1 and produced sVEGFR-1 protein which increased following incubation with tumour necrosis factor α.

Conclusion: This study shows for the first time the presence of sVEGFR-1 in the BAL fluid of patients with ARDS. This may explain the presence of reduced bioactive VEGF in patients early in the course of ARDS.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Compernolle Veerle, Brusselmans Koen, Acker Till, Hoet Peter, Tjwa Marc, Beck Heike, Plaisance Stéphane, Dor Yuval, Keshet Eli, Lupu Florea, et al. 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. 2002 Jul;8(7):702–710. [PubMed]
  • Kaner RJ, Crystal RG. Compartmentalization of vascular endothelial growth factor to the epithelial surface of the human lung. Mol Med. 2001 Apr;7(4):240–246. [PMC free article] [PubMed]
  • Mura Marco, dos Santos Claudia C, Stewart Duncan, Liu Mingyao. Vascular endothelial growth factor and related molecules in acute lung injury. J Appl Physiol (1985) 2004 Nov;97(5):1605–1617. [PubMed]
  • Kupferminc MJ, Daniel Y, Englender T, Baram A, Many A, Jaffa AJ, Gull I, Lessing JB. Vascular endothelial growth factor is increased in patients with preeclampsia. Am J Reprod Immunol. 1997 Oct;38(4):302–306. [PubMed]
  • Thickett DR, Armstrong L, Millar AB. Vascular endothelial growth factor (VEGF) in inflammatory and malignant pleural effusions. Thorax. 1999 Aug;54(8):707–710. [PMC free article] [PubMed]
  • Thickett DR, Armstrong L, Christie SJ, Millar AB. Vascular endothelial growth factor may contribute to increased vascular permeability in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001 Nov 1;164(9):1601–1605. [PubMed]
  • Koyama Sekiya, Sato Etsuro, Haniuda Masayuki, Numanami Hiroki, Nagai Sonoko, Izumi Takateru. Decreased level of vascular endothelial growth factor in bronchoalveolar lavage fluid of normal smokers and patients with pulmonary fibrosis. Am J Respir Crit Care Med. 2002 Aug 1;166(3):382–385. [PubMed]
  • Kanazawa Hiroshi, Asai Kazuhisa, Hirata Kazuto, Yoshikawa Junichi. Possible effects of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease. Am J Med. 2003 Apr 1;114(5):354–358. [PubMed]
  • Meyer KC, Cardoni AL, Xiang Z, Cornwell RD, Love RB. Vascular endothelial growth factor in human lung transplantation. Chest. 2001 Jan;119(1):137–143. [PubMed]
  • Thickett David R, Armstrong Lynne, Millar Ann B. A role for vascular endothelial growth factor in acute and resolving lung injury. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1332–1337. [PubMed]
  • Maitre B, Boussat S, Jean D, Gouge M, Brochard L, Housset B, Adnot S, Delclaux C. Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury. Eur Respir J. 2001 Jul;18(1):100–106. [PubMed]
  • Ohwada A, Yoshioka Y, Iwabuchi K, Nagaoka I, Dambara T, Fukuchi Y. VEGF regulates the proliferation of acid-exposed alveolar lining epithelial cells. Thorax. 2003 Apr;58(4):328–332. [PMC free article] [PubMed]
  • Park WY, Goodman RB, Steinberg KP, Ruzinski JT, Radella F, 2nd, Park DR, Pugin J, Skerrett SJ, Hudson LD, Martin TR. Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1896–1903. [PubMed]
  • Robinson CJ, Stringer SE. The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci. 2001 Mar;114(Pt 5):853–865. [PubMed]
  • Kendall RL, Thomas KA. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10705–10709. [PMC free article] [PubMed]
  • Ferrara Napoleone, Frantz Gretchen, LeCouter Jennifer, Dillard-Telm Lisa, Pham Thinh, Draksharapu Aparna, Giordano Thomas, Peale Franklin. Differential expression of the angiogenic factor genes vascular endothelial growth factor (VEGF) and endocrine gland-derived VEGF in normal and polycystic human ovaries. Am J Pathol. 2003 Jun;162(6):1881–1893. [PMC free article] [PubMed]
  • Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L, Lamy M, Marini JJ, Matthay MA, Pinsky MR, et al. The American-European Consensus Conference on ARDS, part 2. Ventilatory, pharmacologic, supportive therapy, study design strategies and issues related to recovery and remodeling. Intensive Care Med. 1998 Apr;24(4):378–398. [PubMed]
  • Rowan KM, Kerr JH, Major E, McPherson K, Short A, Vessey MP. Intensive Care Society's APACHE II study in Britain and Ireland--I: Variations in case mix of adult admissions to general intensive care units and impact on outcome. BMJ. 1993 Oct 16;307(6910):972–977. [PMC free article] [PubMed]
  • Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993 Dec 22;270(24):2957–2963. [PubMed]
  • Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, LeGall JR, Morris A, Spragg R. Report of the American-European Consensus conference on acute respiratory distress syndrome: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Consensus Committee. J Crit Care. 1994 Mar;9(1):72–81. [PubMed]
  • Rennard SI, Basset G, Lecossier D, O'Donnell KM, Pinkston P, Martin PG, Crystal RG. Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Appl Physiol (1985) 1986 Feb;60(2):532–538. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Holter JF, Weiland JE, Pacht ER, Gadek JE, Davis WB. Protein permeability in the adult respiratory distress syndrome. Loss of size selectivity of the alveolar epithelium. J Clin Invest. 1986 Dec;78(6):1513–1522. [PMC free article] [PubMed]
  • Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L, Lamy M, Marini JJ, Matthay MA, Pinsky MR, et al. The American-European Consensus Conference on ARDS, part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Acute respiratory distress syndrome. Am J Respir Crit Care Med. 1998 Apr;157(4 Pt 1):1332–1347. [PubMed]
  • Pugin J, Verghese G, Widmer MC, Matthay MA. The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome. Crit Care Med. 1999 Feb;27(2):304–312. [PubMed]
  • Kaner RJ, Ladetto JV, Singh R, Fukuda N, Matthay MA, Crystal RG. Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema. Am J Respir Cell Mol Biol. 2000 Jun;22(6):657–664. [PubMed]
  • Toi Masakazu, Bando Hiroko, Ogawa Taeko, Muta Mariko, Hornig Carsten, Weich Herbert A. Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor-1 relationship in breast cancer. Int J Cancer. 2002 Mar 1;98(1):14–18. [PubMed]
  • Kasahara Y, Tuder RM, Taraseviciene-Stewart L, Le Cras TD, Abman S, Hirth PK, Waltenberger J, Voelkel NF. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest. 2000 Dec;106(11):1311–1319. [PMC free article] [PubMed]
  • Tuder Rubin M, Zhen Lijie, Cho Chung Y, Taraseviciene-Stewart Laima, Kasahara Yasunori, Salvemini Daniela, Voelkel Norbert F, Flores Sonia C. Oxidative stress and apoptosis interact and cause emphysema due to vascular endothelial growth factor receptor blockade. Am J Respir Cell Mol Biol. 2003 Jul;29(1):88–97. [PubMed]
  • Ferrara Napoleone, Gerber Hans-Peter, LeCouter Jennifer. The biology of VEGF and its receptors. Nat Med. 2003 Jun;9(6):669–676. [PubMed]
  • Luque Alfonso, Carpizo Darren R, Iruela-Arispe M Luisa. ADAMTS1/METH1 inhibits endothelial cell proliferation by direct binding and sequestration of VEGF165. J Biol Chem. 2003 Jun 27;278(26):23656–23665. [PubMed]
  • Inoki Isao, Shiomi Takayuki, Hashimoto Gakuji, Enomoto Hiroyuki, Nakamura Hiroyuki, Makino Ken-ichi, Ikeda Eiji, Takata Shigeo, Kobayashi Ken-ichi, Okada Yasunori. Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis. FASEB J. 2002 Feb;16(2):219–221. [PubMed]
  • Bhattacharjee G, Asplin IR, Wu SM, Gawdi G, Pizzo SV. The conformation-dependent interaction of alpha 2-macroglobulin with vascular endothelial growth factor. A novel mechanism of alpha 2-macroglobulin/growth factor binding. J Biol Chem. 2000 Sep 1;275(35):26806–26811. [PubMed]

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