ROLE OF MOLECULES OF ANGIOGENESIS IN INTERSTITIAL LUNG DISEASES

DOI: https://doi.org/None

E.N. Popova (1), A.B. Ponomarev (1), E.M. Paltseva (2), M.V. Lebedeva (1), E.A. Kazina (1), I.A. Popova (1) 1 -I.M. Sechenov First Moscow State Medical University, Trubetskaya Str., 8, Moscow, 119991, Russian Federation; 2 -B.V. Petrovsky Russian Surgery Research Center, Abrikosovskiy by-street, 2, Moscow, 119991, Russian Federation

Introduction. In interstitial lung diseases (ILD), characterized by inflammatory and fibrous processes, the intensification of angiogenesis also occurs. The aim of our research. Was the study of characteristics of expression angiogenic molecules (VEGF, ET1) in some ILD variants at different stages of their progression. Methods. standard clinical examination of patients with different ILD types, determination of VEGF and ET1 blood levels by the method of immunosorbent assay; morphological survey of lung biopsies and identification of VEGF expression by the method of immunohistochemistry. Results. VEGF and ET1 blood concentration in all patients with ILD was significantly higher in comparison with control and correlated with the degree of fibrosis according to computer tomography data. The intensity of angiogenesis was detected by the assessment of VEGF expression correlated with VEGF and ET1 blood concentrations and with the grade of fibrosis. The association of the wall thickness of remodeled vessels and VEGF and ET1 blood levels is revealed. Reliable difference between groups of ILD patients with signs of disease activity and without them is shown in dependence of VEGF and ET1 levels. Conclusion. These data demonstrate that VEGF and ET1 play an important role in the ILD progression as markers of endothelial dysfunction and angiogenesis.
Keywords: 
interstitial lung diseases, fibrosis, angiogenesis, vascular endothelial growth factor, endothelin-1, sarcoidosis

Список литературы: 
  1. Kogan E.A., Kornev B.M., Popova E.N., Fomin V.V. i dr. Pod red. N.A. Muhina. Intersticial`nye bolezni legkih: Prakticheskoe rukovodstvo. M.: Litera, 2007; 432 s. [Kogan E.A., Kornev B.M., Popova E.N., Fomin V.V. et al. Under ed. N.A. Mukhin. Interstitial pulmonary diseases: Practical guide. M.: Litera, 2007; 432 p. (in Russian)]
  2. Abraham D. Role of endothelin in lung fibrosis. Eur. Respir. Rev. 2008; 17 (109): 145–50.
  3. ATS statement: guidelines for the six minute walk test. Am. J. Respir. Crit. Care Med. 2002; 166: 111–7.
  4. Wells U, Hirani N. Interstitial lung disease guideline. Thorax. 2008; 63 (5): 1–58.
  5. Popova E.N. Idiopaticheskiy fibroziruyushhiy al`veolit i intersticial`nye pnevmonii. Klin. med. 2005; 6: 21–7. [Popova E.N. Idiopathic fibrosing alveolitis and interstitial pneumonias. Clin. Med. 2005; 6: 21–7 (in Russian)]
  6. Chan SY., Loscalzo J. Pathogenic Mechanisms of Pulmonary Arterial Hypertension. J. Mol. Cell Cardiol. 2008; 44 (1): 14–30.
  7. Chaudhary N.I., Roth G.J., Hilberg F., Müller-Quernheim J., Prasse A., Zissel G. et al. Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis. Eur. Respir. J. 2007; 29: 976–85.
  8. Farkas L., Farkas D., Ask K., Möller A., Gauldie J., Margetts P. et al. VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats. J. Clin. Invest. 2009; 119 (5): 1298–311.
  9. Bikfalvi A. Angiogenesis: molecular mechanisms of activation, promotion and maintenance. J. BUON. 2007; 12 (1): 59–66.
  10. Stenmark KR., Fagan KA., Frid MG. Hypoxia-Induced Pulmonary Vascular Remodeling. Cell. Mol. Mechanisms. Circ Res. 2006; 99: 675–91.
  11. Ferrara N. Vascular endothelial growth factor: Basic science and clinical progress. Endocrine Reviews. 2004; 25 (4): 581–611.
  12. Hamada N., Kuwano K., Yamada M., Hagimoto N., Hiasa K., Egashira K. et al. Anti-vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice. J. Immunol. 2005; 175: 1224–123.
  13. Montani D., Souza R., Binkert C., Fischli W., Simonneau G., Clozel M., Humbert M. Endothelin-1/Endothelin-3 Ratio. A Potential Prognostic Factor of Pulmonary Arterial Hypertension. Chest. 2007; 131: 101–8.
  14. Voelkel N.F., Vandivier R.W., Tuber R.M. Vascular endothelial growth factor in the lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 2006; 290: 209–21.
  15. Walsh DA. Pathophysiological mechanisms of angiogenesis. Adv. Clin. Chem. 2007; 44: 187–221.
  16. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. Eur. Heart J. 2004; 25: 2243–78.
  17. Budhiraja R., Tuder R.M., Hassoun P.M. Endothelial dysfunction in pulmonary hypertension. Circulation. 2004; 109: 159–65.
  18. Nakayama S., Mukae H., Ishii H., Kakugawa T., Sugiyama K., Sakamoto N. et al. Comparison of BALF concentrations of ENA-78 and IP10 in patients with idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Respir. Med. 2005; 99: 1145–51.
  19. Uguccioni M., Pulsatelli L., Grigolo B., Facchini A., Fasano L., Cinti C. et al. Endothelin-1 in idiopathic pulmonary fibrosis. J. Clin. Pathol. 1995; 48: 330–4.
  20. Ventetuolo C.E., Kawut S.M., Lederer D.J. Plasma endothelin-1 and vascular endothelial growth factor levels and their relationship to hemodynamics in idiopathic pulmonary fibrosis. Respiration. 2012; 84 (4): 299-305.
  21. Borensztajn K., Crestani B., Kolb M. Idiopathic pulmonary fibrosis: from epithelial injury to biomarkers – insights from the bench side. Respiration. 2013; 86: 441–52.
  22. Tolnay E., Kuhnen C., Voss B., Wiethege T., Müller K.M. Expression and localization of vascular endothelial growth factor and its receptor flt in pulmonary sarcoidosis. Virchows Arch. 1998; 432 (1): 61–5.