Abstract
Endostatin is an angiogenesis inhibitor that is an endogenously produced proteolytic fragment of type XVIII collagen. Serum levels of endostatin have been studied extensively in patients with malignant diseases. Recently, elevated serum endostatin levels were observed in patients with systemic sclerosis accompanying pulmonary fibrosis. To determine whether elevated serum endostatin can be observed in patients with idiopathic pulmonary fibrosis (IPF), we measured serum levels of endostatin in 69 patients with benign respiratory disease using an ELISA kit. The median of the serum endostatin levels in these patients was 50.8 pg/mL. Seven of 11 patients (63.6%) with collagen disease‐associated pulmonary fibrosis (CDPF), and 19 of 24 patients (79.2%) with IPF had higher serum endostatin levels than the median level of the 69 patients. There was no statistical difference in serum endostatin levels between the patients with IPF and those with CDPF (P=0.7898). Serum endostatin levels in 24 patients with IPF were significantly higher than those in 34 patients with respiratory diseases other than IPF and CDPF (P=0.0001). Elevated serum levels of endostatin were observed in patients with IPF. Although the mechanisms are unclear, elevated serum levels of endostatin may be related to the fibrosing process in the lung. J. Clin. Lab. Anal. 19:146–149, 2005. © 2005 Wiley‐Liss, Inc.
Keywords: idiopathic pulmonary fibrosis, serum, endostatin, collagen disease, chronic obstructive pulmonary disease
REFERENCES
- 1. Feldman AL, Tamarkin L, Paciotti GF, et al. Serum endostatin levels are elevated and correlate with serum vascular endothelial growth factor levels in patients with stage VI renal cancer. Clin Cancer Res 2000;6:4628–4634. [PubMed] [Google Scholar]
- 2. Homer JJ, Greenman J, Stafford ND. Circulating angiogenic cytokines as tumor markers and prognostic factors in head and neck squamous cell carcinoma. Clin Otolaryngol 2002;27:32–37. [DOI] [PubMed] [Google Scholar]
- 3. Suzuki M, Iizasa T, Ko E, et al. Serum endostatin correlates with progression and prognosis of non‐small cell lung cancer. Lung Cancer 2002;35:29–34. [DOI] [PubMed] [Google Scholar]
- 4. Hebbar M, Peyrat J, Hornez L, Hatron P, Hachulla E, Devulder B. Increased concentrations of the circulating angiogenesis inhibitor endostatin in patients with systemic sclerosis. Arthritis Rhem 2000;43:889–893. [DOI] [PubMed] [Google Scholar]
- 5. Distler O, Neidhart M, Gay S. The molecular control of angiogenesis. Int Rev Immunol 2002;21:33–49. [DOI] [PubMed] [Google Scholar]
- 6. Crystal RG, Fulmer JD, Roberts WC, Moss ML, Line BR, Reynolds HY. Idiopathic pulmonary fibrosis: clinical, histologic, radiographic, physiologic, scintigraphic, cytologic, and biochemical aspects. Ann Intern Med 1976;85:769–788. [DOI] [PubMed] [Google Scholar]
- 7. Bjoraker JA, Ryu JH, Edwin MK, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998;157:199–203. [DOI] [PubMed] [Google Scholar]
- 8. Gay SE, Kazerooni EA, Toews GB, et al. Idiopathic pulmonary fibrosis: predicting response to therapy and survival. Am J Respir Crit Care Med 1998;157:1063–1072. [DOI] [PubMed] [Google Scholar]
- 9. Michaelson JE, Aguyo SM, Roman JR. Idiopathic pulmonary fibrosis. Chest 2000;118:788–794. [DOI] [PubMed] [Google Scholar]
- 10. Fitzgerald JE, King TE, Lynch DA, Tuder RM, Schwarz MI. Diffuse panbronchiolitis in the United States. Am J Respir Crit Care Med 1996;154:497–503. [DOI] [PubMed] [Google Scholar]
- 11. Brugiere O, Milleron B, Antoine M, Carette MF, Philippe C, Mayaud C. Diffuse panbronchiolitis in an Asian immigrant. Thorax 1996;51:1065–1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Arnett FC, Edworthy SM, Bloch DA. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–347. [DOI] [PubMed] [Google Scholar]
- 13. Bohan A, Peter JB. Polymyositis and dermatomyositis. N Engl J Med 1975;292:344–347. [DOI] [PubMed] [Google Scholar]
- 14. Vitali C, Bombardieli S, Moutsopoulos HM, et al. Preliminary criteria for the classification of Sjogren's syndrome: results of a prospective concerned action supported by the European Community. Arthritis Rheum 1993;36:340–347. [DOI] [PubMed] [Google Scholar]
- 15. Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee . Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 1980;23:581–590. [DOI] [PubMed] [Google Scholar]
- 16. Kasugawa R. Preliminary diagnostic criteria for classification of mixed connective tissue disease In: Kasugawa R, Sharp GC, editors. Mixed connective tissue disease and anti‐nuclear antibodies. Amsterdam: Excerpta Medica; 1987. p 41–47. [Google Scholar]
- 17. O'Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1977;88:277–285. [DOI] [PubMed] [Google Scholar]
- 18. Sasaki T, Fukai N, Mann K, Gohring W, Olsen BR, Timpl R. Structure, function and tissue forms of the C‐terminal globular domain of collagen XVIII containing the angiogenesis inhibitor endostatin. EMBO J 1998;17:4249–4256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Standker L, Schrader M, Kanse SM, Jurgens M, Forssman WG, Preissner KT. Isolation and characterization of the circulating form of human endostatin. FEBS Lett 1997;29:129–133. [DOI] [PubMed] [Google Scholar]
- 20. Kanazawa H, Asai K, Hirata K, Yoshikawa J. Possible effects of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease. Am J Med 2003;114:354–358. [DOI] [PubMed] [Google Scholar]