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01-07-2004 | Original Article

Elevated levels of vascular endothelial growth factor in serum of patients with D+ HUS

Authors: D. Maroeska te Loo, Nienke Bosma, Victor van Hinsbergh, Paul Span, Rob de Waal, Ruud Clarijs, C. Sweep, Leo Monnens, Lambertus van den Heuvel

Published in: Pediatric Nephrology | Issue 7/2004

Abstract

The pathogenesis of hemolytic uremic syndrome (D+ HUS) is characterized by endothelial damage of glomeruli and tubules within the kidney. In several other diseases in which glomerular endothelial damage occurs, elevated serum levels of vascular endothelial growth factor (VEGF) have been reported. VEGF is involved in angiogenesis, permeabilization of blood vessel endothelium, and wound repair. In this study we evaluated VEGF levels in the serum of 40 D+ HUS patients in the acute phase and during the course of the disease. VEGF levels were measured using a double-sandwich ELISA. Indirect immunohistochemistry was performed for the detection of VEGF in renal biopsy material of 3 HUS patients. Significantly elevated VEGF levels were found in HUS patients compared with controls in both serum (P<0.001) and plasma (P<0.05). A significant relationship was found between VEGF levels and severity of the disease according to the classification of Gianantonio (P<0.05). Levels of VEGF in blood increased during the 2nd and 3rd week after HUS was diagnosed. Immunohistochemistry of renal biopsy material showed increased levels of the receptors for VEGF in the glomeruli. During the course of HUS, plasma VEGF levels increase and the increase is dependent on the severity of the disease. This is probably associated with the repair process.

Ferrara N (1999) Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Int 56:794–814CrossRefPubMed

Ferrara N, Davis-Smyth (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25PubMed

Smith LE, Kopchick JJ, Chen W, Knapp J, Kinose F, Daley D, Foley E, Smith RG, Schaeffer JM (1997) Essential role of growth hormone in ischemia-induced retinal neovascularization. Science 276:1706–1709CrossRefPubMed

Pupilli C, Lasagni L, Romagnani P, Bellini F, Manelli M, Misciglia N, Mavilia C, Vellei U, Villari D, Serio M (1999) Angiotensin II stimulates the synthesis and secretion of vascular permeability factor/vascular endothelial growth factor in human mesangial cells. J Am Soc Nephrol 10:245–255CrossRefPubMed

Salven P, Orpana A, Joensuu H (1999) Leukocytes and platelets of patients with cancer contain high levels of vascular endothelial growth factor. Clin Cancer Res 5:487–491PubMed

Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9–22PubMed

Kaplan BS, Cleary TG, Obrig TG (1990) Recent advances in understanding the pathogenesis of the hemolytic uremic syndromes. Pediatr Nephrol 4:276–283PubMed

Siegler RL (1995) The hemolytic uremic syndrome. Pediatr Clin North Am 42:1505–1529

Karmali MA, Petric M, Lim C, Fleming PC, Arbus GS, Lior H (1985) The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli. J Infect Dis 151:775–782PubMed

10.

Setten PA van, Hinsbergh VW van, Velden TJ van der, Kar NC van de, Vermeer M, Mahan JD, Assmann KJ, Heuvel LP van den, Monnens LA (1997) Effects of TNF alpha on verocytotoxin cytotoxicity in purified human glomerular microvascular endothelial cells. Kidney Int 51:1245–1256PubMed

11.

Ohno T, Igarashi H, Inoue K, Akazawa JOH, Hara T (2000) Serum vascular endothelial growth factor: a new predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease. Eur J Pediatr 159:424–429CrossRefPubMed

12.

Hayman R, Brockelsby J, Kenny L, Baker P (1999) Preeclampsia: the endothelium, circulating factor(s) and vascular endothelial growth factor. J Soc Gynecol Invest 6:3–10CrossRef

13.

Gianantonio C, Vitacco M, Mendilaharzu F, Gallo G, Sojo E (1973) The hemolytic-uremic syndrome. Nephron 11:174–192PubMed

14.

Maloney JP, Silliman CC, Ambruso DR, Wang J, Tuder RM, Voelkel NF (1998) In vitro release of vascular endothelial growth factor during platelet aggregation. Am J Physiol 275:1054–1061

15.

Webb NJ, Bottomley MJ, Watson CJ, Brenchley PE (1998) Vascular endothelial growth factor (VEGF) is released from platelets during blood clotting: implications for measurement of circulating VEGF levels in clinical disease. Clin Sci (Colch) 94:395–404

16.

Span PN, Grebenchtchikov N, Geurts-Moespot J, Westphal JR, Lucassen AM, Sweep CG (2000) EORTC receptor and biomarker study group report: a sandwich enzyme-linked immunosorbent assay for vascular endothelial growth factor in blood and tumor tissue extracts. Int J Biol Markers 15:184–191PubMed

17.

Kerstens HM, Poddighe PJ, Hanselaar AG (1995) A novel in situ hybridization signal amplification method based on the deposition of biotinylated tyramine. J Histochem Cytochem 43:347–352PubMed

18.

Tufro A, Norwood VF, Carey RM, Gomez RA (1999) Vascular endothelial growth factor induces nephrogenesis and vasculogenesis. J Am Soc Nephrol 10:2125–2134PubMed

19.

Whittle C, Gillespie K, Harrison R, Mathieson PW, Harper SJ (1999) Heterogeneous vascular endothelial growth factor (VEGF) isoform mRNA and receptor mRNA expression in human glomeruli, and the identification of VEGF148 mRNA, a novel truncated splice variant. Clin Sci (Colch) 97:303–312

20.

Marx PT, Mulder AB, Bergh FA van den, Overbeeke R, Haanen C, Vermes I (1999) Apoptosis inducers endotoxin and Fas-ligation enhance the expression of vascular endothelial growth factor in human endothelial cells. Endothelium 6:335–340PubMed

21.

Esser S, Wolburg K, Wolburg H, Breier G, Kurzchalia T, Risau W (1998) Vascular endothelial growth factor induces endothelial fenestrations in vitro. J Cell Biol 140:947–959PubMed

22.

Ostendorf T, Kunter U, Eitner F, Loos A, Regele H, Kerjaschki D, Henninger DD, Janjic N, Floege J (1999) VEGF(165) mediates glomerular endothelial repair. J Clin Invest 104:913–923PubMed

23.

Scalia R, Booth G, Lefer DJ (1999) Vascular endothelial growth factor attenuates leukocyte-endothelium interaction during acute endothelial dysfunction: essential role of endothelium-derived nitric oxide. FASEB J 13:1039–1046PubMed

24.

Kim Y, Suga S, Kang D, Jefferson JA, Mazzali M, Gordon KL, Matsui K, Breiteneder-eleff S, Shankland SJ, Hughes J, Kerjaschki D, Schreiner GF, Johnson RJ (2000) Vascular endothelial growth factor accelerates renal recovery in thrombotic microangiopathy. Kidney Int 58:2390–2399CrossRefPubMed

25.

Barleon B, Siemeister G, Martiny-Baron G, Weindel K, Herzog C, Marme D (1997) Vascular endothelial growth factor up-regulates its receptor fms-like tyrosine kinase 1 (FLT-1) and a soluble variant of FLT-1 in human vascular endothelial cells. Cancer Res 57:5421–5425PubMed

26.

Waltenberger J, Mayr U, Pentz S, Hombach V (1996) Functional upregulation of the vascular endothelial growth factor receptor KDR by hypoxia. Circulation 94:1647–1654PubMed

27.

Wang D, Donner DB, Warren RS (2000) Homeostatic modulation of cell surface KDR and Flt1 expression and expression of the vascular endothelial cell growth factor (VEGF) receptor mRNAs by VEGF. J Biol Chem 275:15905–15911CrossRefPubMed

28.

Shulman K, Rosen S, Tognazzi K, Manseau EJ, Brown LF (1996) Expression of vascular permeability factor (VPF/VEGF) is altered in many glomerular diseases. J Am Soc Nephrol 7:661–666PubMed

29.

Nitta K, Uchida K, Kimata N, Honda K, Horita S, Hayashi T, Ishizuka T, Koboyashi I H, Kawashima A, Yumura W, Nihei H (1999) Increased serum levels of vascular endothelial growth factor in human crescentic glomerulonephritis. Clin Nephrol 52:76–82PubMed

30.

Griga T, Werner S, Koller M, Tromm A, May B (1999) Vascular endothelial growth factor (VEGF) in Crohn’s disease: increased production by peripheral blood mononuclear cells and decreased VEGF165 labeling of peripheral CD14+ monocytes. Dig Dis Sci 44:1196–1201CrossRefPubMed

31.

Webb NJ, Myers CR, Watson CJ, Bottomley MJ, Brenchley PE (1998) Activated human neutrophils express vascular endothelial growth factor (VEGF). Cytokine 10:254–257CrossRefPubMed

32.

Taichman NS, Young S, Cruchley AT, Taylor P, Paleologe E (1997) Human neutrophils secrete vascular endothelial growth factor. J Leukoc Biol 62:397–400PubMed

33.

Fitzpatrick MM, Shah V, Trompeter RS, Dillon MJ, Barratt TM (1992) Interleukin-8 and polymorphoneutrophil leucocyte activation in hemolytic uremic syndrome of childhood. Kidney Int 42:951–956PubMed

34.

Fitzpatrick MM, Shah V, Filler G, Dillon MJ, Barratt TM (1992) Neutrophil activation in the haemolytic uraemic syndrome: free and complexed elastase in plasma. Pediatr Nephrol 6:50–53PubMed

35.

Bousvaros A, Leichtner A, Zurakowski D, Kwon J, Law T, Keough K, Fishman S (1999) Elevated serum vascular endothelial growth factor in children and young adults with Crohn’s disease. Dig Dis Sci 44:424–430PubMed

Title: Elevated levels of vascular endothelial growth factor in serum of patients with D+ HUS
Authors: D. Maroeska te Loo
Nienke Bosma
Victor van Hinsbergh
Paul Span
Rob de Waal
Ruud Clarijs
C. Sweep
Leo Monnens
Lambertus van den Heuvel
Publication date: 01-07-2004
Publisher: Springer-Verlag
Published in: Pediatric Nephrology / Issue 7/2004
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-004-1475-3

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Elevated levels of vascular endothelial growth factor in serum of patients with D+ HUS

Abstract

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Abstract

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