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Erschienen in: Lung 3/2010

01.06.2010

Significance of Serum Vascular Endothelial Growth Factor Level in Patients with Idiopathic Pulmonary Fibrosis

verfasst von: Masaru Ando, Eishi Miyazaki, Takeo Ito, Shigeo Hiroshige, Shin-ich Nureki, Takuya Ueno, Ryuichi Takenaka, Tetsujiro Fukami, Toshihide Kumamoto

Erschienen in: Lung | Ausgabe 3/2010

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Abstract

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis, which has been implicated in the pathogenesis of fibrotic lung diseases, including idiopathic pulmonary fibrosis (IPF). The aim of this study was to examine the clinical significance of the serum VEGF level for evaluating disease severity and progression. The levels of VEGF in serum were measured in 41 patients with IPF, 14 patients with lung cancer, and 43 healthy volunteers. We measured the serum levels of CRP, LDH, KL-6, SP-D, and the parameters obtained from arterial blood gas analysis and pulmonary function tests. High-resolution computed tomography (HRCT) was performed to determine the extent of the interstitial and the alveolar opacities. The ability of each biomarker to predict disease severity was estimated by measuring the area under the receiver operating characteristic curve (AUC). The VEGF levels of IPF patients with high alveolar–arterial difference of oxygen (AaDO2) levels were significantly elevated than those with low AaDO2 levels and those of healthy volunteers. When examined within the IPF group, a significant positive correlation was found between the VEGF levels and the HRCT interstitial score (p = 0.027) and the KL-6 levels (p = 0.037). Among several serum biomarkers, VEGF showed the largest AUC for predicting disease severity as defined by a high AaDO2 value. There was an inverse correlation between the baseline VEGF level and the monthly change in percent predicted vital capacity. The serum VEGF level may reflect the severity of IPF and offer clinical benefits to predict the disease’s progression.
Literatur
1.
Zurück zum Zitat American Thoracic Society (2000) Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 161:646–664 American Thoracic Society (2000) Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 161:646–664
2.
Zurück zum Zitat American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias (2002) This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 165:277–304 American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias (2002) This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 165:277–304
3.
Zurück zum Zitat Bjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, Schroeder DR, Offord KP (1998) Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 157:199–203PubMed Bjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, Schroeder DR, Offord KP (1998) Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 157:199–203PubMed
4.
Zurück zum Zitat Yokoyama A, Kondo K, Nakajima M, Matsushima T, Takahashi T, Nishimura M, Bando M, Sugiyama Y, Totani Y, Ishizaki T, Ichiyasu H, Suga M, Hamada H, Kohno N (2006) Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis. Respirology 11:164–168CrossRefPubMed Yokoyama A, Kondo K, Nakajima M, Matsushima T, Takahashi T, Nishimura M, Bando M, Sugiyama Y, Totani Y, Ishizaki T, Ichiyasu H, Suga M, Hamada H, Kohno N (2006) Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis. Respirology 11:164–168CrossRefPubMed
5.
Zurück zum Zitat Takahashi H, Shiratori M, Kanai A, Chiba H, Kuroki Y, Abe S (2006) Monitoring markers of disease activity for interstitial lung diseases with serum surfactant proteins A and D. Respirology 11(Suppl):S51–S54CrossRefPubMed Takahashi H, Shiratori M, Kanai A, Chiba H, Kuroki Y, Abe S (2006) Monitoring markers of disease activity for interstitial lung diseases with serum surfactant proteins A and D. Respirology 11(Suppl):S51–S54CrossRefPubMed
6.
Zurück zum Zitat Satoh H, Kurishima K, Ishikawa H, Ohtsuka M (2006) Increased levels of KL-6 and subsequent mortality in patients with interstitial lung diseases. J Intern Med 260:429–434CrossRefPubMed Satoh H, Kurishima K, Ishikawa H, Ohtsuka M (2006) Increased levels of KL-6 and subsequent mortality in patients with interstitial lung diseases. J Intern Med 260:429–434CrossRefPubMed
7.
Zurück zum Zitat Ward PA, Hunninghake GW (1998) Lung inflammation and fibrosis. Am J Respir Crit Care Med 157:S123–S129PubMed Ward PA, Hunninghake GW (1998) Lung inflammation and fibrosis. Am J Respir Crit Care Med 157:S123–S129PubMed
8.
Zurück zum Zitat Kamp DW (2003) Idiopathic pulmonary fibrosis the inflammation hypothesis revisited. Chest 124:1187–1190CrossRefPubMed Kamp DW (2003) Idiopathic pulmonary fibrosis the inflammation hypothesis revisited. Chest 124:1187–1190CrossRefPubMed
9.
Zurück zum Zitat Magro CM, Allen J, Pope-Harman A, Waldman WJ, Moh P, Rothrauff S, Ross P Jr (2003) The role of microvascular injury in the evolution of idiopathic pulmonary fibrosis. Am J Clin Pathol 119:556–567CrossRefPubMed Magro CM, Allen J, Pope-Harman A, Waldman WJ, Moh P, Rothrauff S, Ross P Jr (2003) The role of microvascular injury in the evolution of idiopathic pulmonary fibrosis. Am J Clin Pathol 119:556–567CrossRefPubMed
10.
Zurück zum Zitat Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J (2000) Vascular-specific growth factors and blood vessel formation. Nature 407:242–248CrossRefPubMed Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J (2000) Vascular-specific growth factors and blood vessel formation. Nature 407:242–248CrossRefPubMed
11.
Zurück zum Zitat Koyama S, Sato E, Haniuda M, Numanami H, Nagai S, Izumi T (2002) 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 166:382–385CrossRefPubMed Koyama S, Sato E, Haniuda M, Numanami H, Nagai S, Izumi T (2002) 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 166:382–385CrossRefPubMed
12.
Zurück zum Zitat Cosgrove GP, Brown KK, Schiemann WP, Serls AE, Parr JE, Geraci MW, Schwarz MI, Cool CD, Worthen GS (2004) Pigment epithelium-derived factor in idiopathic pulmonary fibrosis: a role in aberrant angiogenesis. Am J Respir Crit Care Med 170:242–251CrossRefPubMed Cosgrove GP, Brown KK, Schiemann WP, Serls AE, Parr JE, Geraci MW, Schwarz MI, Cool CD, Worthen GS (2004) Pigment epithelium-derived factor in idiopathic pulmonary fibrosis: a role in aberrant angiogenesis. Am J Respir Crit Care Med 170:242–251CrossRefPubMed
13.
Zurück zum Zitat Meyer KC, Cardoni A, Xiang ZZ (2000) Vascular endothelial growth factor in bronchoalveolar lavage from normal subjects and patients with diffuse parenchymal lung disease. J Lab Clin Med 135:332–338CrossRefPubMed Meyer KC, Cardoni A, Xiang ZZ (2000) Vascular endothelial growth factor in bronchoalveolar lavage from normal subjects and patients with diffuse parenchymal lung disease. J Lab Clin Med 135:332–338CrossRefPubMed
14.
Zurück zum Zitat Gay SE, Kazerooni EA, Toews GB, Lynch JP 3rd, Gross BH, Cascade PN, Spizarny DL, Flint A, Schork MA, Whyte RI, Popovich J, Hyzy R, Martinez FJ (1998) Idiopathic pulmonary fibrosis: predicting response to therapy and survival. Am J Respir Crit Care Med 157:1063–1072PubMed Gay SE, Kazerooni EA, Toews GB, Lynch JP 3rd, Gross BH, Cascade PN, Spizarny DL, Flint A, Schork MA, Whyte RI, Popovich J, Hyzy R, Martinez FJ (1998) Idiopathic pulmonary fibrosis: predicting response to therapy and survival. Am J Respir Crit Care Med 157:1063–1072PubMed
15.
Zurück zum Zitat Suzuma K, Naruse K, Suzuma I, Takahara N, Ueki K, Aiello LP, King GL (2000) Vascular endothelial growth factor induces expression of connective tissue growth factor via KDR, Flt1, and phosphatidylinositol 3-kinase-akt-dependent pathways in retinal vascular cells. J Biol Chem 275:40725–40731CrossRefPubMed Suzuma K, Naruse K, Suzuma I, Takahara N, Ueki K, Aiello LP, King GL (2000) Vascular endothelial growth factor induces expression of connective tissue growth factor via KDR, Flt1, and phosphatidylinositol 3-kinase-akt-dependent pathways in retinal vascular cells. J Biol Chem 275:40725–40731CrossRefPubMed
16.
Zurück zum Zitat Wang H, Keiser JA (1998) Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells: role of flt-1. Circ Res 83:832–840PubMed Wang H, Keiser JA (1998) Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells: role of flt-1. Circ Res 83:832–840PubMed
17.
Zurück zum Zitat Hamada N, Kuwano K, Yamada M, Hagimoto N, Hiasa K, Egashira K, Nakashima N, Maeyama T, Yoshimi M, Nakanishi Y (2005) Anti-vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice. J Immunol 175:1224–1231PubMed Hamada N, Kuwano K, Yamada M, Hagimoto N, Hiasa K, Egashira K, Nakashima N, Maeyama T, Yoshimi M, Nakanishi Y (2005) Anti-vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice. J Immunol 175:1224–1231PubMed
18.
Zurück zum Zitat Ou XM, Li WC, Liu DS, Li YP, Wen FQ, Feng YL, Zhang SF, Huang XY, Wang T, Wang K, Wang X, Chen L (2009) VEGFR-2 antagonist SU5416 attenuates bleomycin-induced pulmonary fibrosis in mice. Int Immunopharmacol 9:70–79CrossRefPubMed Ou XM, Li WC, Liu DS, Li YP, Wen FQ, Feng YL, Zhang SF, Huang XY, Wang T, Wang K, Wang X, Chen L (2009) VEGFR-2 antagonist SU5416 attenuates bleomycin-induced pulmonary fibrosis in mice. Int Immunopharmacol 9:70–79CrossRefPubMed
19.
Zurück zum Zitat 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 164:1601–1605PubMed 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 164:1601–1605PubMed
20.
Zurück zum Zitat Simler NR, Brenchley PE, Horrocks AW, Greaves SM, Hasleton PS, Egan JJ (2004) Angiogenic cytokines in patients with idiopathic interstitial pneumonia. Thorax 59:581–585CrossRefPubMed Simler NR, Brenchley PE, Horrocks AW, Greaves SM, Hasleton PS, Egan JJ (2004) Angiogenic cytokines in patients with idiopathic interstitial pneumonia. Thorax 59:581–585CrossRefPubMed
21.
Zurück zum Zitat Ohnishi H, Yokoyama A, Kondo K, Hamada H, Abe M, Nishimura K, Hiwada K, Kohno N (2002) Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med 165:378–381PubMed Ohnishi H, Yokoyama A, Kondo K, Hamada H, Abe M, Nishimura K, Hiwada K, Kohno N (2002) Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med 165:378–381PubMed
22.
Zurück zum Zitat Kobayashi J, Kitamura S (1996) Serum KL-6 for the evaluation of active pneumonitis in pulmonary sarcoidosis. Chest 109:1276–1282CrossRefPubMed Kobayashi J, Kitamura S (1996) Serum KL-6 for the evaluation of active pneumonitis in pulmonary sarcoidosis. Chest 109:1276–1282CrossRefPubMed
23.
Zurück zum Zitat Kohno N, Awaya Y, Oyama T, Yamakido M, Akiyama M, Inoue Y, Yokoyama A, Hamada H, Fujioka S, Hiwada K (1993) KL-6, a mucin-like glycoprotein, in bronchoalveolar lavage fluid from patients with interstitial lung disease. Am Rev Respir Dis 148:637–642PubMed Kohno N, Awaya Y, Oyama T, Yamakido M, Akiyama M, Inoue Y, Yokoyama A, Hamada H, Fujioka S, Hiwada K (1993) KL-6, a mucin-like glycoprotein, in bronchoalveolar lavage fluid from patients with interstitial lung disease. Am Rev Respir Dis 148:637–642PubMed
24.
Zurück zum Zitat Inoue Y, Barker E, Daniloff E, Kohno N, Hiwada K, Newman LS (1997) Pulmonary epithelial cell injury and alveolar-capillary permeability in berylliosis. Am J Respir Crit Care Med 156:109–115PubMed Inoue Y, Barker E, Daniloff E, Kohno N, Hiwada K, Newman LS (1997) Pulmonary epithelial cell injury and alveolar-capillary permeability in berylliosis. Am J Respir Crit Care Med 156:109–115PubMed
25.
Zurück zum Zitat Collard HR, King TE Jr, Bartelson BB, Vourlekis JS, Schwarz MI, Brown KK (2003) Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 168:538–542CrossRefPubMed Collard HR, King TE Jr, Bartelson BB, Vourlekis JS, Schwarz MI, Brown KK (2003) Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 168:538–542CrossRefPubMed
26.
Zurück zum Zitat Flaherty KR, Mumford JA, Murray S, Kazerooni EA, Gross BH, Colby TV, Travis WD, Flint A, Toews GB, Lynch JP 3rd, Martinez FJ (2003) Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med 168:543–548CrossRefPubMed Flaherty KR, Mumford JA, Murray S, Kazerooni EA, Gross BH, Colby TV, Travis WD, Flint A, Toews GB, Lynch JP 3rd, Martinez FJ (2003) Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med 168:543–548CrossRefPubMed
Metadaten
Titel
Significance of Serum Vascular Endothelial Growth Factor Level in Patients with Idiopathic Pulmonary Fibrosis
verfasst von
Masaru Ando
Eishi Miyazaki
Takeo Ito
Shigeo Hiroshige
Shin-ich Nureki
Takuya Ueno
Ryuichi Takenaka
Tetsujiro Fukami
Toshihide Kumamoto
Publikationsdatum
01.06.2010
Verlag
Springer-Verlag
Erschienen in
Lung / Ausgabe 3/2010
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-009-9223-x

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