Нефротический синдром: роль ангиопоэтинов в патогенезе
Аннотация
Сосудистые эндотелиальные факторы роста, обеспечивающие ангио- и васкулогенез, играют важнейшую роль в физиологии и патологии человека. Влияя на функции эндотелия, ангиопоэтины способствуют образованию первичных кровеносных сосудов у эмбриона, а у взрослых способствуют заживлению ран, улучшают коллатеральную циркуляцию при инфаркте миокарда, ускоряя реабилитацию пациентов. В то же время ангиопоэтины индуцируют целый ряд неблагоприятных эффектов: развитие диабетической ретинопатии, макулярной дегенерации сетчатки, ускоряют рост и метастазирование злокачественных опухолей. В обзоре приводятся данные о роли агиопоэтинов (VEGF-A и ANGPTL4) в патогенезе основных проявлений нефротического синдрома - протеинурии, отеков, дислипидемии. Установлено, что экспрессия гипосиализированной формы ANGPTL4 в подоцитах способна вызывать развитие нефротического синдрома и гипертриглицеридемии у больных диабетической нефропатией и гломерулонефритом с минимальными изменениями. Однако на фоне продолжающихся потерь белка с мочой повышается экспрессия ANGPTL4 в сердце, печени, мышцах, уменьшающая протеинурию, но одновременно усугубляющая гипертриглицеридемию. В то же время мутантные формы ANGPTL4 индуцируют ремиссию нефротического синдрома, не ухудшая липидный профиль. Назначение больным N-ацетил-D-маннозамина способно трансформировать гипосиализированный ANGPTL4 в нормальный и существенно снижать протеинурию и предупреждать рецидивы нефротического синдрома.
Об авторах
В. М. Ермоленко
ГБОУ ДПО РМАПО Минздрава РФ
Россия
Россия
Н. Н. Филатова
ГБОУ ДПО РМАПО Минздрава РФ
Россия
Россия
Список литературы
1. Andersen H, Friis UG, Hansen PB et al. Diabetic nephropathy is associated with increased urine excretion of proteases plasmin, prostasin and urokinase and activation of amiloride-sensitive current in collecting duct cells. Nephrol Dial Transplant. 2015. 30(5): 781-9.
2. Banai S, Shweiki D, Pinson A et al. Upregulation of vascular endothelial growth factor expression induced by myocardial ischaemia: implications for coronary angiogenesis. Cardiovasc Res. 1994. 28(8): 1176-9.
3. Bertuccio C, Veron D, Aggarwal PK et al. Vascular endothelial growth factor receptor 2 direct interaction with nephrin links VEGF-A signals to actin in kidney podocytes. J Biol Chem. 2011. 286(46): 39933-44.
4. Buhl KB, Friis UG, Svenningsen P et al. Urinary plasmin activates collecting duct ENaC current in preeclampsia. Hypertension. 2012. 60(5): 1346-51.
5. Butterworth MB, Zhang L, Heidrich EM et al. Activation of the epithelial sodium channel (ENaC) by the alkaline protease from Pseudomonas aeruginosa. J Biol Chem. 2012. 287(39): 32556-65.
6. Caldwell RA, Boucher RC, Stutts MJ. Neutrophil elastase activates near-silent epithelial Na+ channels and increases airway epithelial Na+ transport. Am J Physiol Lung Cell Mol Physiol. 2005. 288(5): L813-9.
7. Carmeliet P, Ferreira V, Breier G et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996. 380(6573): 435-9.
8. Chandra M, Hoyer JR, Lewy JE. Renal function in rats with unilateral proteinuria produced by renal perfusion with aminonucleoside. Pediatr Res. 1981. 15(4 Pt 1): 340-4.
9. Chraibi A, Vallet V, Firsov D et al. Protease modulation of the activity of the epithelial sodium channel expressed in Xenopus oocytes. J Gen Physiol. 1998. 111(1): 127-38.
10. Chugh SS, Clement LC, Mace C. New insights into human minimal change disease: lessons from animal models. Am J Kidney Dis. 2012. 59(2): 284-92.
11. Chugh SS, Mace C, Clement LC et al. Angiopoietin-like 4 based therapeutics for proteinuria and kidney disease. Front Pharmacol. 2014. 5: 23.
12. Clement LC, Avila-Casado C, Mace C et al. Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome. Nat Med. 2011. 17(1): 117-22.
13. Clement LC, Liu G, Perez-Torres I et al. Early changes in gene expression that influence the course of primary glomerular disease. Kidney Int. 2007. 72(3): 337-47.
14. Clement LC, Mace C, Avila-Casado C et al. Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome. Nat Med. 2014. 20(1): 37-46.
15. De Sain-van der Velden MG, Kaysen GA, Barrett HA et al. Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis. Kidney Int. 1998. 53(4): 994-1001.
16. De Vriese AS, Tilton RG, Elger M, Stephan CC, Kriz W, Lameire NH. Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. J Am Soc Nephrol. 2001. 12(5): 993-1000.
17. Deschenes G, Feraille E, Doucet A. Mechanisms of oedema in nephrotic syndrome: old theories and new ideas. Nephrol Dial Transplant. 2003. 18(3): 454-6.
18. Du Bray ES. Metabolism: The Status of Lipoid Nephrosis as a Clinical Entity. Cal West Med. 1928. 29(1): 47-8.
19. Earley LE, Forland M. Nephrotic syndrome. In: Strauss and Welt’s Diseases of the Kidney. Edited by Earley LE, Gottschalk CW, Boston, Little, Brown and Company. 1979, pp 765-813.
20. Eremina V, Cui S, Gerber H et al. Vascular endothelial growth factor a signaling in the podocyte-endothelial compartment is required for mesangial cell migration and survival. J Am Soc Nephrol. 2006. 17(3): 724-35.
21. Eremina V, Jefferson JA, Kowalewska J et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med. 2008. 358(11): 1129-36.
22. Eremina V, Sood M, Haigh J et al. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest. 2003. 111(5): 707-16.
23. Fan Q, Xing Y, Ding J, Guan N. Reduction in VEGF protein and phosphorylated nephrin associated with proteinuria in adriamycin nephropathy rats. Nephron Exp Nephrol. 2009. 111(4): e92-e102.
24. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989. 161(2): 851-8.
25. Geers AB, Koomans HA, Boer P, Dorhout Mees EJ. Plasma and blood volumes in patients with the nephrotic syndrome. Nephron. 1984. 38(3): 170-3.
26. Georgiadi A, Lichtenstein L, Degenhardt T et al. Induction of cardiac Angptl4 by dietary fatty acids is mediated by peroxisome proliferator-activated receptor beta/delta and protects against fatty acid-induced oxidative stress. Circ Res. 2010. 106(11): 1712-21.
27. Ghiggeri GM, Ginevri F, Candiano G et al. Characterization of cationic albumin in minimal change nephropathy. Kidney Int. 1987. 32(4): 547-53.
28. Gurevich F, Perazella MA. Renal effects of anti-angiogenesis therapy: update for the internist. Am J Med. 2009. 122(4): 322-8.
29. Hara A, Wada T, Furuichi K et al. Blockade of VEGF accelerates proteinuria, via decrease in nephrin expression in rat crescentic glomerulonephritis. Kidney Int. 2006. 69(11): 1986-95.
30. Hohenstein B, Hausknecht B, Boehmer K et al. Local VEGF activity but not VEGF expression is tightly regulated during diabetic nephropathy in man. Kidney Int. 2006. 69(9): 1654-61.
31. Hughey RP, Bruns JB, Kinlough CL et al. Epithelial sodium channels are activated by furin-dependent proteolysis. J Biol Chem. 2004. 279(18): 18111-4.
32. Ichikawa I, Rennke HG, Hoyer JR et al. Role for intrarenal mechanisms in the impaired salt excretion of experimental nephrotic syndrome. J Clin Invest. 1983. 71(1): 91-103.
33. Johnson RJ, Herrera-Acosta J, Schreiner GF, Rodriguez-Iturbe B. Subtle acquired renal injury as a mechanism of salt-sensitive hypertension. N Engl J Med. 2002. 346(12): 913-23.
34. Kampen KR. The mechanisms that regulate the localization and overexpression of VEGF receptor-2 are promising therapeutic targets in cancer biology. Anticancer Drugs. 2012. 23(4): 347-54.
35. Kersten S, Lichtenstein L, Steenbergen E et al. Caloric restriction and exercise increase plasma ANGPTL4 levels in humans via elevated free fatty acids. Arterioscler Thromb Vasc Biol. 2009. 29(6): 969-74.
36. Kersten S, Mandard S, Tan NS et al. Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. J Biol Chem. 2000. 275(37): 28488-93.
37. Kim I, Kim HG, Kim H et al. Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis. Biochem J. 2000. 346 Pt 3: 603-10.
38. Kirk R. Nephrotic syndrome: Negative feedback loop reveals novel potential therapy. Nat Rev Nephrol. 2014. 10(2): 63.
39. Kleyman TR, Hughey RP. Plasmin and sodium retention in nephrotic syndrome. J Am Soc Nephrol. 2009. 20(2): 233-4.
40. Klisic J, Zhang J, Nief V et al. Albumin regulates the Na+/H+ exchanger 3 in OKP cells. J Am Soc Nephrol. 2003. 14(12): 3008-16.
41. Koliwad SK, Kuo T, Shipp LE et al. Angiopoietin-like 4 (ANGPTL4, fasting-induced adipose factor) is a direct glucocorticoid receptor target and participates in glucocorticoid-regulated triglyceride metabolism. J Biol Chem. 2009. 284(38): 25593-601.
42. Koot BG, Houwen R, Pot DJ, Nauta J. Congenital analbuminaemia: biochemical and clinical implications. A case report and literature review. Eur J Pediatr. 2004. 163(11): 664-70.
43. Lerique B, Moulin B, Delpero C et al. High-affinity interaction of long-chain fatty acids with serum albumin in nephrotic syndrome. Clin Sci (Lond). 1995. 89(4): 417-20.
44. Liang KH, Oveisi F, Vaziri ND. Gene expression of hepatic cholesterol 7 alpha-hydroxylase in the course of puromycin-induced nephrosis. Kidney Int. 1996. 49(3): 855-60.
45. Mackenzie F, Ruhrberg C. Diverse roles for VEGF-A in the nervous system. Development. 2012. 139(8): 1371-80.
46. Maharaj AS, Saint-Geniez M, Maldonado AE, D'Amore PA. Vascular endothelial growth factor localization in the adult. Am J Pathol. 2006. 168(2): 639-48.
47. Muller F. Verhand. der Deutsch. Path. Gesellschaft 64-69 (1905).
48. Nakagawa T. Uncoupling of the VEGF-endothelial nitric oxide axis in diabetic nephropathy: an explanation for the paradoxical effects of VEGF in renal disease. Am J Physiol Renal Physiol. 2007. 292(6): F1665-72.
49. Ness GC, Chambers CM. Feedback and hormonal regulation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase: the concept of cholesterol buffering capacity. Proc Soc Exp Biol Med. 2000. 224(1): 8-19.
50. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999. 13(1): 9-22.
51. Padua D, Zhang XH, Wang Q et al. TGF-beta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell. 2008. 133(1): 66-77.
52. Palmer BF, Alpern RJ. Pathogenesis of edema formation in the nephrotic syndrome. Kidney Int Suppl. 59: S21-7.
53. Passero CJ, Mueller GM, Rondon-Berrios H et al. Plasmin activates epithelial Na+ channels by cleaving the gamma subunit. J Biol Chem. 2008. 283(52): 36586-91.
54. Peng JH, Feng Y, Rhodes PG. Down-regulation of phospholipase D2 mRNA in neonatal rat brainstem and cerebellum after hypoxia-ischemia. Neurochem Res. 2006. 31(10): 1191-6.
55. Picard N, Eladari D, El Moghrabi S et al. Defective ENaC processing and function in tissue kallikrein-deficient mice. J Biol Chem. 2008. 283(8): 4602-11.
56. Piedagnel R, Tiger Y, Lelongt B, Ronco PM. Urokinase (u-PA) is produced by collecting duct principal cells and is post-transcriptionally regulated by SV40 large-T, arginine vasopressin, and epidermal growth factor. J Cell Physiol. 2006. 206(2): 394-401.
57. Reiser J. Filtering new facts about kidney disease. Nat Med. 2011. 17(1): 44-5.
58. Rodriguez-Iturbe B, Herrera-Acosta J, Johnson RJ. Interstitial inflammation, sodium retention, and the pathogenesis of nephrotic edema: a unifying hypothesis. Kidney Int. 2002. 62(4): 1379-84.
59. Rothschild MA, Oratz M, Schreiber SS. Albumin synthesis. 1. N Engl J Med. 1972. 286(14): 748-57.
60. Sabia PJ, Powers ER, Ragosta M et al. An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction. N Engl J Med. 1992. 327(26): 1825-31.
61. Schlondorff D. Putting the glomerulus back together: per aspera ad astra ("a rough road leads to the stars"). Kidney Int. 2014. 85(5): 991-8.
62. Schrijvers BF, Flyvbjerg A, De Vriese AS. The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int. 2004. 65(6): 2003-17.
63. Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992. 359(6398): 843-5.
64. Sison K, Eremina V, Baelde H et al. Glomerular structure and function require paracrine, not autocrine, VEGF-VEGFR-2 signaling. J Am Soc Nephrol. 2010. 21(10): 1691-701.
65. Staiger H, Haas C, Machann J et al. Muscle-derived angiopoietin-like protein 4 is induced by fatty acids via peroxisome proliferator-activated receptor (PPAR)-delta and is of metabolic relevance in humans. Diabetes. 2009. 58(3): 579-89.
66. Stockmann C, Doedens A, Weidemann A et al. Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis. Nature. 2008. 456(7223): 814-8.
67. Svenningsen P, Bistrup C, Friis UG et al. Plasmin in nephrotic urine activates the epithelial sodium channel. J Am Soc Nephrol. 2009. 20(2): 299-310.
68. Vaziri ND, Gonzales EC, Shayestehfar B, Barton CH. Plasma levels and urinary excretion of fibrinolytic and protease inhibitory proteins in nephrotic syndrome. J Lab Clin Med. 1994. 124(1): 118-24.
69. Vaziri ND, Liang KH. Down-regulation of hepatic LDL receptor expression in experimental nephrosis. Kidney Int. 1996. 50(3): 887-93.
70. Vaziri ND, Sato T, Liang K. Molecular mechanisms of altered cholesterol metabolism in rats with spontaneous focal glomerulosclerosis. Kidney Int. 2003. 63(5): 1756-63.
71. Vaziri ND. Molecular mechanisms of lipid disorders in nephrotic syndrome. Kidney Int. 2003. 63(5): 1964-76.
72. Veron D, Reidy KJ, Bertuccio C et al. Overexpression of VEGF-A in podocytes of adult mice causes glomerular disease. Kidney Int. 2010. 77(11): 989-99.
73. Vuagniaux G, Vallet V, Jaeger NF et al. Synergistic activation of ENaC by three membrane-bound channel-activating serine proteases (mCAP1, mCAP2, and mCAP3) and serum- and glucocorticoid-regulated kinase (Sgk1) in Xenopus Oocytes. J Gen Physiol. 2002. 120(2): 191-201.
74. Wagner SN, Atkinson MJ, Wagner C et al. Sites of urokinase-type plasminogen activator expression and distribution of its receptor in the normal human kidney. Histochem Cell Biol. 1996. 105(1): 53-60.
75. Watanabe D, Suzuma K, Suzuma I et al. Vitreous levels of angiopoietin 2 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Am J Ophthalmol. 2005. 139(3): 476-81.
76. Wiesner G, Morash BA, Ur E, Wilkinson M. Food restriction regulates adipose-specific cytokines in pituitary gland but not in hypothalamus. J Endocrinol. 2004. 180(3): R1-6.
77. Yoon JC, Chickering TW, Rosen ED et al. Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. Mol Cell Biol. 2000. 20(14): 5343-9.
78. Ziyadeh FN, Wolf G. Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. Curr Diabetes Rev. 2008. 4(1): 39-45.
Рецензия
Для цитирования:
Ермоленко В.М., Филатова Н.Н. Нефротический синдром: роль ангиопоэтинов в патогенезе. Нефрология и диализ. 2016;18(4):387-393.
For citation:
Ermolenko V.M., Filatova N.N. Nephrotic syndrome: role of the angiopoietins in the pathogenesis. Nephrology and Dialysis. 2016;18(4):387-393. (In Russ.)
Просмотров:
45
Послать статью по эл. почте 