Белок сосудистой адгезии-1 (VAP-1) и его роль в моделировании воспалительного процесса и фиброза. Нефрологический вектор

Существует семейство белков, локализованных на клеточных поверхностях и регулирующих процесс лимфоцит-эндотелиоцитарного взаимодействия, именуемых эктопептиды. К их числу относится и VAP-1 (vascular adhesive protein-1, белок сосудистой адгезии-1). Человеческий VAP-1 является димерным мембранным белком с молекулярной массой 180 кДа, состоящим из короткого N-концевого цитоплазматического хвоста, трансмембранного домена и большой внеклеточной части. VAP-1 стимулирует прокатку (роллинг), адгезию и диапедез (трансмиграцию) лимфоцитов через эндотелиальную выстилку сосудов, а также полиморфно-ядерных лейкоцитов. При изучении экспрессии VAP-1 в почках он обнаруживается в эндотелиальных клетках перитубулярных капилляров и перицитах, а также гладкомышечных клетках более крупных сосудов. Практически полностью отсутствует экспрессия VAP-1 в эндотелии почечных клубочков. Дальнейшее изучение влияния сигнального VAP-1-опосредованного пути на течение и исходы гломерулонефрита позволит расширить представления о патогенезе заболевания и новых путях влияния на прогрессирование хронической болезни почек.

белок сосудистой адгезии-1 (VAP-1), семикарбазид-чувствительная аминоксидаза (SSAO), перитубулярные сосуды, перитубулярный фиброз, хроническая болезнь почек

1. Salmi M, Jalkanen S. A 90-kilodalton endothelial cell molecule mediating lymphocyte binding in humans. Science 1992; 257· 1407-1409

2. Rucker RB, O’Dell BL. Connective tissue amine oxidase I. Purification of bovine aorta amine oxidase and its comparison with plasma amine oxidase. Biochim Biophys Acta Enzymol 1971; 235·32-43

3. Airenne TT, Nymalm X Kidron H et al. Crystal structure of the human vascular adhesion protein-1· Unique structural features with functional implications. Protein Science 2005; 14·1964-1974.

4. Jalkanen S, Salmi M. Cell surface monoamine oxidases· enzymes in search of a function. EMBO J. 2001; 20· 3893-3901

5. Abella A, Garcia-Vicente S, Viguerie N et al. Adipocytes release a soluble form of VAP-1/SSAO by a metalloprotease-dependent process and in a regulated manner. Diabetologia 2004; 47· 429-438

6. Kurkijarvi R, Adams DH, Leino R et al. Circulating form of human vascular adhesion protein-1 (VAP-1)· increased serum levels in inflammatory liver diseases. J Immunol 1998; 161· 1549-1557

7. Salmi M, Jalkanen S. Developmental regulation of the adhesive and enzymatic activity of vascular adhesion protein-1 (VAP-1) in humans. Blood. 2006; 108· 1555-1561

8. Tohka S, Laukkanen M-L, Jalkanen S, Salmi M. Vascular adhesion protein 1 (VAP-1) functions as a molecular brake during granulocyte rolling and mediates their recruitment in vivo. FASEB J. 2001; 15· 373-382

9. Salmi M, Yegutkin GG, Lehvonen R et al. A cell surface amine oxidase directly controls lymphocyte migration. Immunity 2001; 14· 265-276

10. Dunkel P, Balogh B, Meleddu R et al. Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1· a patent survey. Expert Opin. Ther. Patents 2011; 21(9)· 1453-1471

11. Kinemuchi H, Sugimoto H, Obata T, Satoh N, Ueda S. Selective inhibitors of membrane-bound semicarbazide-sensitive amine oxidase (SSAO) activity in mammalian tissues. Neurotoxicology. 2004; 25· 325-335

12. Merinen M, Irjala H, Salmi M et al. Vascular adhesion protein-1 is involved in both acute and chronic inflammation in the mouse. Am J Pathol. 2005; 166· 793-800

13. Koskinen K, Vainio PJ, Smith DJ et al. Granulocyte transmigration through the endothelium is regulated by the oxidase activity of vascular adhesion protein-1 (VAP-1). Blood 2004; 103· 3388-3395

14. Noonan T, Lukas S, Peet GW et al. The oxidase activity of vascular adhesion protein-1 (VAP-1) is essential for function. Am. J. Clin. Exp. Immunol. 2013; 2(2)· 172-185

15. Galkina E, Ley K. Vascular Adhesion Molecules in Atherosclerosis. Arterioscler Thromb Vasc Biol. 2007; 27· 2292-2301

16. Jalkanen S, Karikoski M, Mercier N et al. The oxidase activity of vascular adhesion protein-1 (VAP-1) induces endothelial E- and P-selectins and leukocyte binding. Blood. 2007; 110· 1864 -1870

17. Morin N, Lizcano JM, Fontana E et al. Semicarbazide-sensitive amineoxidase substrates stimulate glucose transport and inhibit lipolysis in human adipocytes. J Pharmacol Exp Ther 2001; 297· 563-572

18. Carpene C, Bour S, Visentin V et al. Amine oxidase substrates for impaired glucose tolerance correction. J Physiol Biochem 2005; 61· 405-420

19. Iffiu-Soltesz Z, Wanecq E, Lomba A et al. Chronic benzylamine administration in the drinking water improves glucose tolerance, reduces body weight gain and circulating cholesterol in high-fat diet-fed mice. Pharmacol Res 2010; 61· 355-363

20. Mercader J, Iffiu-Soltesz Z, Brenachot X et al. SSAO substrates exhibiting insulin-like effects in adipocytes as a promising treatment option for metabolic disorders. Future MedChem 2010; 2· 1735-1749

21. Noda K, She H, Nakazawa T et al. Vascular adhesion protein-1 blockade suppresses choroidal neovascularization. FASEB J 2008; 22· 2928-2935

22. Kurkijärvi R, Jalkanen S, Isoniemi H, Salmi M. Vascular adhesion protein-1 (VAP-1) mediates lymphocyte-endothelial interactions in chronic kidney rejection. Eur. J. Immunol. 2001. 31· 2876-2884

23. Boomsma F, Veldhuisen DJ van, Kam PJ et al. Plasma semicarbazide-sensitive amine oxidase is elevated in patients with congestive heart failure. Cardiovasc Res 1997; 33· 387-391

24. Airas L, Mikkola J, Vainio JM et al. Elevated serum soluble vascular adhesion protein-1 (VAP-1) in patients with active relapsing remitting multiple sclerosis. J of Neuroimmunology 2006; 177· 132-135

25. Koc-Zorawska E, Malyszko J, Zbroch E et al. Vascular adhesion protein-1 and renalase in regard to diabetes in hemodialysis patients. Arch Med Sci 2012; 8(6)· 1048-1052

26. Koc-Zorawska E, Malyszko J, Zbroch E et al. VAP-1 in peritoneally dialyzed patients. Postepy Hig Med Dosw (Online). 2013; 67· 1340-134

27. Lin M-S, Li H-Y Wei J-N et al. Serum vascular adhesion protein-1 is higher in subjects with early stages of chronic kidney disease. Clinical Biochemistry 2008; (41)· 1362-1367

28. Lin S., Kisseleva T, Brenner DA, Duffield JS. Pericytes and perivascular fibroblasts are the primary source of collagen-producing cells in obstructive fibrosis of the kidney. Am J Pathol 2008; 173· 1617-1627

29. Kawakami T, Mimura I, Shoji K et al. Hypoxia and fibrosis in chronic kidney disease· crossing at pericytes. Kidney Int Suppl 2014; (4)· 107-112

30. Epstein FH. Oxygen and renal metabolism. Kidney Int 1997;51· 381-385

31. Lin SL, Chang FC, Schrimpf C et al. Targeting endothelium-pericyte cross talk by inhibiting VEGF receptor signaling attenuates kidney microvascular rarefaction and fibrosis. Am J Pathol. 2011; 178·911-923

32. Schrimpf C, Teebken OE, Wilhelmi M, Duffield JS. The Role of Pericyte Detachment in Vascular Rarefaction. J Vasc Res 2014; 51· 247-258

33. Nakao S, Noda K, Zandi S et al. VAP-1-Mediated M2 Macrophage Infiltration Underlies IL-1 β - but Not VEGF-A-Induced Lymph- and Angiogenesis. Am J Pathol 2011; 178· 1913-1921

34. Foot JS, Yow TT, Schilter H et al. PXS-4681A, a Potent and Selective Mechanism-Based Inhibitor of SSAO/VAP-1 with Anti-Inflammatory Effects In Vivo. J Pharmacol Exp Ther 2013; 347· 365-374