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Published in: Pediatric Nephrology 5/2012

01-05-2012 | Original Article

Soluble VEGF receptor 1 promotes endothelial injury in children and adolescents with lupus nephritis

Authors: Monika Edelbauer, Sudhir Kshirsagar, Magdalena Riedl, Heiko Billing, Burkhard Tönshoff, Dieter Haffner, Jörg Dötsch, Gottfried Wechselberger, Lutz T. Weber, Elisabeth Steichen-Gersdorf

Published in: Pediatric Nephrology | Issue 5/2012

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Abstract

Background

Endothelial cell injury plays a key role in the pathogenesis of lupus nephritis (LN) and atherosclerosis. The aim of this study was to identify factors involved in the process of endothelial damage in children and adolescents with LN.

Methods

We evaluated the relationship between plasma vascular endothelial growth factor (VEGF), its soluble receptors sVEGFR-1 and sVEGFR-2 and markers of endothelial inflammation and injury (angiopoietin-2 and thrombomodulin, respectively) in 23 children and adolescents with LN (active LN, n = 14; inactive LN, n = 9; mean age 15 years) and 20 healthy controls (HC; mean age 12 years).

Results

VEGF, sVEGFR-1, angiopoietin-2 and thrombomodulin levels were significantly higher in children and adolescents with active LN than in patients in remission or HC. In active LN, however, VEGF was inversely related to sVEGFR-1 (r = −0.802, p < 0.001), angiopoietin-2 (r = −0.684, p = 0.007) and thrombomodulin (r = −0.697, p = 0.006). There was a significant positive correlation between sVEGFR-1 and thrombomodulin (r = 0.814, p < 0.0001), but sVEGFR-2 did not significantly differ between the patient groups and did not correlate with thrombomodulin (r = 0.046, p = 0.833).

Conclusions

sVEGFR-1 may play an important role in promoting endothelial damage in children and adolescents with active LN and could possibly be used to monitor disease severity.
Literature
1.
go back to reference Appel GB, Pirani CL, D'Agati V (1994) Renal vascular complications of systemic lupus erythematosus. J Am Soc Nephrol 4:1499–1515PubMed Appel GB, Pirani CL, D'Agati V (1994) Renal vascular complications of systemic lupus erythematosus. J Am Soc Nephrol 4:1499–1515PubMed
2.
go back to reference Banfi G, Bertani T, Boeri V, Faraggiana T, Mazzucco G, Monga G, Sacchi G (1991) Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). Am J Kidney Dis 18:240–248PubMed Banfi G, Bertani T, Boeri V, Faraggiana T, Mazzucco G, Monga G, Sacchi G (1991) Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). Am J Kidney Dis 18:240–248PubMed
3.
go back to reference Rajagopalan S, Somers EC, Brook RD, Kehrer C, Pfenninger D, Lewis E, Chakrabarti A, Richardson BC, Shelden E, McCune WJ, Kaplan MJ (2004) Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity. Blood 103:3677–3683PubMedCrossRef Rajagopalan S, Somers EC, Brook RD, Kehrer C, Pfenninger D, Lewis E, Chakrabarti A, Richardson BC, Shelden E, McCune WJ, Kaplan MJ (2004) Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity. Blood 103:3677–3683PubMedCrossRef
4.
go back to reference El-Magadmi M, Bodill H, Ahmad Y, Durrington PN, Mackness M, Walker M, Bernstein RM, Bruce IN (2004) Systemic lupus erythematosus: an independent risk factor for endothelial dysfunction in women. Circulation 110:399–404PubMedCrossRef El-Magadmi M, Bodill H, Ahmad Y, Durrington PN, Mackness M, Walker M, Bernstein RM, Bruce IN (2004) Systemic lupus erythematosus: an independent risk factor for endothelial dysfunction in women. Circulation 110:399–404PubMedCrossRef
5.
go back to reference Lee PY, Li Y, Richards HB, Chan FS, Zhuang H, Narain S, Butfiloski EJ, Sobel ES, Reeves WH, Segal MS (2007) Type I interferon as a novel risk factor for endothelial progenitor cell depletion and endothelial dysfunction in systemic lupus erythematosus. Arthritis Rheum 56:3759–3769PubMedCrossRef Lee PY, Li Y, Richards HB, Chan FS, Zhuang H, Narain S, Butfiloski EJ, Sobel ES, Reeves WH, Segal MS (2007) Type I interferon as a novel risk factor for endothelial progenitor cell depletion and endothelial dysfunction in systemic lupus erythematosus. Arthritis Rheum 56:3759–3769PubMedCrossRef
6.
go back to reference Kahlenberg JM, Kaplan MJ (2011) The interplay of inflammation and cardiovascular disease in systemic lupus erythematosus. Arthritis Res Ther 13:203PubMedCrossRef Kahlenberg JM, Kaplan MJ (2011) The interplay of inflammation and cardiovascular disease in systemic lupus erythematosus. Arthritis Res Ther 13:203PubMedCrossRef
7.
go back to reference Dimmeler S, Hermann C, Zeiher AM (1998) Apoptosis of endothelial cells. Contribution to the pathophysiology of atherosclerosis? Eur Cytokine Netw 9:697–698PubMed Dimmeler S, Hermann C, Zeiher AM (1998) Apoptosis of endothelial cells. Contribution to the pathophysiology of atherosclerosis? Eur Cytokine Netw 9:697–698PubMed
8.
go back to reference Turesson C, Jacobsson LT, Matteson EL (2008) Cardiovascular co-morbidity in rheumatic diseases. Vasc Health Risk Manag 4:605–614PubMed Turesson C, Jacobsson LT, Matteson EL (2008) Cardiovascular co-morbidity in rheumatic diseases. Vasc Health Risk Manag 4:605–614PubMed
9.
go back to reference McMahon M, Hahn BH, Skaggs BJ (2011) Systemic lupus erythematosus and cardiovascular disease: prediction and potential for therapeutic intervention. Expert Rev Clin Immunol 7:227–241PubMedCrossRef McMahon M, Hahn BH, Skaggs BJ (2011) Systemic lupus erythematosus and cardiovascular disease: prediction and potential for therapeutic intervention. Expert Rev Clin Immunol 7:227–241PubMedCrossRef
10.
go back to reference Roman MJ, Shanker BA, Davis A, Lockshin MD, Sammaritano L, Simantov R, Crow MK, Schwartz JE, Paget SA, Devereux RB, Salmon JE (2003) Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 349:2399–2406PubMedCrossRef Roman MJ, Shanker BA, Davis A, Lockshin MD, Sammaritano L, Simantov R, Crow MK, Schwartz JE, Paget SA, Devereux RB, Salmon JE (2003) Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 349:2399–2406PubMedCrossRef
11.
go back to reference de Leeuw K, Smit AJ, de Groot E, van Roon AM, Kallenberg CG, Bijl M (2009) Longitudinal study on premature atherosclerosis in patients with systemic lupus erythematosus. Atherosclerosis 206:546–550PubMedCrossRef de Leeuw K, Smit AJ, de Groot E, van Roon AM, Kallenberg CG, Bijl M (2009) Longitudinal study on premature atherosclerosis in patients with systemic lupus erythematosus. Atherosclerosis 206:546–550PubMedCrossRef
12.
go back to reference Boros CA, Bradley TJ, Cheung MM, Bargman JM, Russell JL, McCrindle BW, Adeli K, Hamilton J, Silverman ED (2011) Early determinants of atherosclerosis in pediatric systemic lupus erythematosus. Clin Exp Rheumatol 29:575–581PubMed Boros CA, Bradley TJ, Cheung MM, Bargman JM, Russell JL, McCrindle BW, Adeli K, Hamilton J, Silverman ED (2011) Early determinants of atherosclerosis in pediatric systemic lupus erythematosus. Clin Exp Rheumatol 29:575–581PubMed
13.
go back to reference Gerber HP, McMurtrey A, Kowalski J, Yan M, Keyt BA, Dixit V, Ferrara N (1998) Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 273:30336–30343PubMedCrossRef Gerber HP, McMurtrey A, Kowalski J, Yan M, Keyt BA, Dixit V, Ferrara N (1998) Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 273:30336–30343PubMedCrossRef
14.
15.
go back to reference Lee S, Chen TT, Barber CL, Jordan MC, Murdock J, Desai S, Ferrara N, Nagy A, Roos KP, Iruela-Arispe ML (2007) Autocrine VEGF signaling is required for vascular homeostasis. Cell 130:691–703PubMedCrossRef Lee S, Chen TT, Barber CL, Jordan MC, Murdock J, Desai S, Ferrara N, Nagy A, Roos KP, Iruela-Arispe ML (2007) Autocrine VEGF signaling is required for vascular homeostasis. Cell 130:691–703PubMedCrossRef
16.
go back to reference Mor F, Quintana FJ, Cohen IR (2004) Angiogenesis-inflammation cross-talk: vascular endothelial growth factor is secreted by activated T cells and induces Th1 polarization. J Immunol 172:4618–4623PubMed Mor F, Quintana FJ, Cohen IR (2004) Angiogenesis-inflammation cross-talk: vascular endothelial growth factor is secreted by activated T cells and induces Th1 polarization. J Immunol 172:4618–4623PubMed
17.
go back to reference Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25PubMedCrossRef Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25PubMedCrossRef
18.
go back to reference Melter M, Reinders ME, Sho M, Pal S, Geehan C, Denton MD, Mukhopadhyay D, Briscoe DM (2000) Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo. Blood 96:3801–3808PubMed Melter M, Reinders ME, Sho M, Pal S, Geehan C, Denton MD, Mukhopadhyay D, Briscoe DM (2000) Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo. Blood 96:3801–3808PubMed
19.
go back to reference Robak E, Sysa-Jedrzejewska A, Robak T (2003) Vascular endothelial growth factor and its soluble receptors VEGFR-1 and VEGFR-2 in the serum of patients with systemic lupus erythematosus. Mediators Inflamm 12:293–298PubMedCrossRef Robak E, Sysa-Jedrzejewska A, Robak T (2003) Vascular endothelial growth factor and its soluble receptors VEGFR-1 and VEGFR-2 in the serum of patients with systemic lupus erythematosus. Mediators Inflamm 12:293–298PubMedCrossRef
20.
go back to reference Avihingsanon Y, Benjachat T, Tassanarong A, Sodsai P, Kittikovit V, Hirankarn N (2009) Decreased renal expression of vascular endothelial growth factor in lupus nephritis is associated with worse prognosis. Kidney Int 75:1340–1348PubMedCrossRef Avihingsanon Y, Benjachat T, Tassanarong A, Sodsai P, Kittikovit V, Hirankarn N (2009) Decreased renal expression of vascular endothelial growth factor in lupus nephritis is associated with worse prognosis. Kidney Int 75:1340–1348PubMedCrossRef
21.
go back to reference Feliers D (2009) Vascular endothelial growth factor as a prognostic marker of lupus nephritis. Kidney Int 75:1251–1253PubMedCrossRef Feliers D (2009) Vascular endothelial growth factor as a prognostic marker of lupus nephritis. Kidney Int 75:1251–1253PubMedCrossRef
22.
go back to reference Kendall RL, Thomas KA (1993) Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci USA 90:10705–10709PubMedCrossRef Kendall RL, Thomas KA (1993) Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci USA 90:10705–10709PubMedCrossRef
23.
go back to reference Kendall RL, Wang G, Thomas KA (1996) Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. Biochem Biophys Res Commun 226:324–328PubMedCrossRef Kendall RL, Wang G, Thomas KA (1996) Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. Biochem Biophys Res Commun 226:324–328PubMedCrossRef
24.
go back to reference Roeckl W, Hecht D, Sztajer H, Waltenberger J, Yayon A, Weich HA (1998) Differential binding characteristics and cellular inhibition by soluble VEGF receptors 1 and 2. Exp Cell Res 241:161–170PubMedCrossRef Roeckl W, Hecht D, Sztajer H, Waltenberger J, Yayon A, Weich HA (1998) Differential binding characteristics and cellular inhibition by soluble VEGF receptors 1 and 2. Exp Cell Res 241:161–170PubMedCrossRef
25.
go back to reference Ebos JM, Bocci G, Man S, Thorpe PE, Hicklin DJ, Zhou D, Jia X, Kerbel RS (2004) A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma. Mol Cancer Res 2:315–326PubMed Ebos JM, Bocci G, Man S, Thorpe PE, Hicklin DJ, Zhou D, Jia X, Kerbel RS (2004) A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma. Mol Cancer Res 2:315–326PubMed
26.
go back to reference Barleon B, Reusch P, Totzke F, Herzog C, Keck C, Martiny-Baron G, Marme D (2001) Soluble VEGFR-1 secreted by endothelial cells and monocytes is present in human serum and plasma from healthy donors. Angiogenesis 4:143–154PubMedCrossRef Barleon B, Reusch P, Totzke F, Herzog C, Keck C, Martiny-Baron G, Marme D (2001) Soluble VEGFR-1 secreted by endothelial cells and monocytes is present in human serum and plasma from healthy donors. Angiogenesis 4:143–154PubMedCrossRef
27.
go back to reference Hornig C, Barleon B, Ahmad S, Vuorela P, Ahmed A, Weich HA (2000) Release and complex formation of soluble VEGFR-1 from endothelial cells and biological fluids. Lab Invest 80:443–454PubMed Hornig C, Barleon B, Ahmad S, Vuorela P, Ahmed A, Weich HA (2000) Release and complex formation of soluble VEGFR-1 from endothelial cells and biological fluids. Lab Invest 80:443–454PubMed
28.
go back to reference Lorquet S, Berndt S, Blacher S, Gengoux E, Peulen O, Maquoi E, Noel A, Foidart JM, Munaut C, Pequeux C (2010) Soluble forms of VEGF receptor-1 and −2 promote vascular maturation via mural cell recruitment. FASEB J 24:3782–3795PubMedCrossRef Lorquet S, Berndt S, Blacher S, Gengoux E, Peulen O, Maquoi E, Noel A, Foidart JM, Munaut C, Pequeux C (2010) Soluble forms of VEGF receptor-1 and −2 promote vascular maturation via mural cell recruitment. FASEB J 24:3782–3795PubMedCrossRef
29.
go back to reference Pavlakovic H, Becker J, Albuquerque R, Wilting J, Ambati J (2010) Soluble VEGFR-2: an antilymphangiogenic variant of VEGF receptors. Ann N Y Acad Sci 1207[Suppl 1]:E7–15PubMedCrossRef Pavlakovic H, Becker J, Albuquerque R, Wilting J, Ambati J (2010) Soluble VEGFR-2: an antilymphangiogenic variant of VEGF receptors. Ann N Y Acad Sci 1207[Suppl 1]:E7–15PubMedCrossRef
30.
go back to reference Oh H, Takagi H, Suzuma K, Otani A, Matsumura M, Honda Y (1999) Hypoxia and vascular endothelial growth factor selectively up-regulate angiopoietin-2 in bovine microvascular endothelial cells. J Biol Chem 274:15732–15739PubMedCrossRef Oh H, Takagi H, Suzuma K, Otani A, Matsumura M, Honda Y (1999) Hypoxia and vascular endothelial growth factor selectively up-regulate angiopoietin-2 in bovine microvascular endothelial cells. J Biol Chem 274:15732–15739PubMedCrossRef
31.
go back to reference Fiedler U, Scharpfenecker M, Koidl S, Hegen A, Grunow V, Schmidt JM, Kriz W, Thurston G, Augustin HG (2004) The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood 103:4150–4156PubMedCrossRef Fiedler U, Scharpfenecker M, Koidl S, Hegen A, Grunow V, Schmidt JM, Kriz W, Thurston G, Augustin HG (2004) The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood 103:4150–4156PubMedCrossRef
32.
go back to reference Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, Gale NW, Witzenrath M, Rosseau S, Suttorp N, Sobke A, Herrmann M, Preissner KT, Vajkoczy P, Augustin HG (2006) Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med 12:235–239PubMedCrossRef Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, Gale NW, Witzenrath M, Rosseau S, Suttorp N, Sobke A, Herrmann M, Preissner KT, Vajkoczy P, Augustin HG (2006) Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med 12:235–239PubMedCrossRef
33.
go back to reference Scharpfenecker M, Fiedler U, Reiss Y, Augustin HG (2005) The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through an internal autocrine loop mechanism. J Cell Sci 118:771–780PubMedCrossRef Scharpfenecker M, Fiedler U, Reiss Y, Augustin HG (2005) The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through an internal autocrine loop mechanism. J Cell Sci 118:771–780PubMedCrossRef
34.
go back to reference Boffa MC, Karmochkine M (1998) Thrombomodulin: an overview and potential implications in vascular disorders. Lupus 7[Suppl 2]:S120–125PubMedCrossRef Boffa MC, Karmochkine M (1998) Thrombomodulin: an overview and potential implications in vascular disorders. Lupus 7[Suppl 2]:S120–125PubMedCrossRef
35.
go back to reference Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725PubMedCrossRef Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725PubMedCrossRef
36.
go back to reference Doria A, Vesco P, Zulian F, Gambari PF (1994) The 1982 ARA/ACR criteria for the classification of systemic lupus erythematosus in pediatric and adult patients. Clin Exp Rheumatol 12:689–690PubMed Doria A, Vesco P, Zulian F, Gambari PF (1994) The 1982 ARA/ACR criteria for the classification of systemic lupus erythematosus in pediatric and adult patients. Clin Exp Rheumatol 12:689–690PubMed
37.
go back to reference Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JA, Cook T, Ferrario F, Fogo AB, Ginzler EM, Hebert L, Hill G, Hill P, Jennette JC, Kong NC, Lesavre P, Lockshin M, Looi LM, Makino H, Moura LA, Nagata M (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 15:241–250PubMedCrossRef Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JA, Cook T, Ferrario F, Fogo AB, Ginzler EM, Hebert L, Hill G, Hill P, Jennette JC, Kong NC, Lesavre P, Lockshin M, Looi LM, Makino H, Moura LA, Nagata M (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 15:241–250PubMedCrossRef
38.
go back to reference Brunner HI, Feldman BM, Bombardier C, Silverman ED (1999) Sensitivity of the Systemic Lupus Erythematosus Disease Activity Index, British Isles Lupus Assessment Group Index, and Systemic Lupus Activity Measure in the evaluation of clinical change in childhood-onset systemic lupus erythematosus. Arthritis Rheum 42:1354–1360PubMedCrossRef Brunner HI, Feldman BM, Bombardier C, Silverman ED (1999) Sensitivity of the Systemic Lupus Erythematosus Disease Activity Index, British Isles Lupus Assessment Group Index, and Systemic Lupus Activity Measure in the evaluation of clinical change in childhood-onset systemic lupus erythematosus. Arthritis Rheum 42:1354–1360PubMedCrossRef
39.
go back to reference Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMed Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMed
40.
go back to reference Narshi CB, Giles IP, Rahman A (2011) The endothelium: an interface between autoimmunity and atherosclerosis in systemic lupus erythematosus? Lupus 20:5–13PubMedCrossRef Narshi CB, Giles IP, Rahman A (2011) The endothelium: an interface between autoimmunity and atherosclerosis in systemic lupus erythematosus? Lupus 20:5–13PubMedCrossRef
41.
go back to reference Cines DB, Lyss AP, Reeber M, Bina M, DeHoratius RJ (1984) Presence of complement-fixing anti-endothelial cell antibodies in systemic lupus erythematosus. J Clin Invest 73:611–625PubMedCrossRef Cines DB, Lyss AP, Reeber M, Bina M, DeHoratius RJ (1984) Presence of complement-fixing anti-endothelial cell antibodies in systemic lupus erythematosus. J Clin Invest 73:611–625PubMedCrossRef
42.
go back to reference Belmont HM, Abramson SB, Lie JT (1996) Pathology and pathogenesis of vascular injury in systemic lupus erythematosus. Interactions of inflammatory cells and activated endothelium. Arthritis Rheum 39:9–22PubMedCrossRef Belmont HM, Abramson SB, Lie JT (1996) Pathology and pathogenesis of vascular injury in systemic lupus erythematosus. Interactions of inflammatory cells and activated endothelium. Arthritis Rheum 39:9–22PubMedCrossRef
44.
go back to reference Ostendorf T, Kunter U, Eitner F, Loos A, Regele H, Kerjaschki D, Henninger DD, Janjic N, Floege J (1999) VEGF mediates glomerular endothelial repair. J Clin Invest 104:913–923PubMedCrossRef Ostendorf T, Kunter U, Eitner F, Loos A, Regele H, Kerjaschki D, Henninger DD, Janjic N, Floege J (1999) VEGF mediates glomerular endothelial repair. J Clin Invest 104:913–923PubMedCrossRef
45.
go back to reference Eremina V, Sood M, Haigh J, Nagy A, Lajoie G, Ferrara N, Gerber HP, Kikkawa Y, Miner JH, Quaggin SE (2003) Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest 111:707–716PubMed Eremina V, Sood M, Haigh J, Nagy A, Lajoie G, Ferrara N, Gerber HP, Kikkawa Y, Miner JH, Quaggin SE (2003) Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest 111:707–716PubMed
46.
go back to reference Caccamo C, Nostro L, Giorgianni G, Mondello S, Crasci E, Frisina N, Buemi M (2007) Behavior of vascular endothelial growth factor and erythropoietin throughout the menstrual cycle in healthy women. J Reprod Med 52:1035–1039PubMed Caccamo C, Nostro L, Giorgianni G, Mondello S, Crasci E, Frisina N, Buemi M (2007) Behavior of vascular endothelial growth factor and erythropoietin throughout the menstrual cycle in healthy women. J Reprod Med 52:1035–1039PubMed
47.
go back to reference Schiffer L, Bethunaickan R, Ramanujam M, Huang W, Schiffer M, Tao H, Madaio MP, Bottinger EP, Davidson A (2008) Activated renal macrophages are markers of disease onset and disease remission in lupus nephritis. J Immunol 180:1938–1947PubMed Schiffer L, Bethunaickan R, Ramanujam M, Huang W, Schiffer M, Tao H, Madaio MP, Bottinger EP, Davidson A (2008) Activated renal macrophages are markers of disease onset and disease remission in lupus nephritis. J Immunol 180:1938–1947PubMed
48.
go back to reference Guo Q, Carrero JJ, Yu X, Barany P, Qureshi AR, Eriksson M, Anderstam B, Chmielewski M, Heimburger O, Stenvinkel P, Lindholm B, Axelsson J (2009) Associations of VEGF and its receptors sVEGFR-1 and −2 with cardiovascular disease and survival in prevalent haemodialysis patients. Nephrol Dial Transplant 24:3468–3473PubMedCrossRef Guo Q, Carrero JJ, Yu X, Barany P, Qureshi AR, Eriksson M, Anderstam B, Chmielewski M, Heimburger O, Stenvinkel P, Lindholm B, Axelsson J (2009) Associations of VEGF and its receptors sVEGFR-1 and −2 with cardiovascular disease and survival in prevalent haemodialysis patients. Nephrol Dial Transplant 24:3468–3473PubMedCrossRef
49.
go back to reference Ebos JM, Lee CR, Bogdanovic E, Alami J, Van Slyke P, Francia G, Xu P, Mutsaers AJ, Dumont DJ, Kerbel RS (2008) Vascular endothelial growth factor-mediated decrease in plasma soluble vascular endothelial growth factor receptor-2 levels as a surrogate biomarker for tumor growth. Cancer Res 68:521–529PubMedCrossRef Ebos JM, Lee CR, Bogdanovic E, Alami J, Van Slyke P, Francia G, Xu P, Mutsaers AJ, Dumont DJ, Kerbel RS (2008) Vascular endothelial growth factor-mediated decrease in plasma soluble vascular endothelial growth factor receptor-2 levels as a surrogate biomarker for tumor growth. Cancer Res 68:521–529PubMedCrossRef
50.
go back to reference Davis B, Dei Cas A, Long DA, White KE, Hayward A, Ku CH, Woolf AS, Bilous R, Viberti G, Gnudi L (2007) Podocyte-specific expression of angiopoietin-2 causes proteinuria and apoptosis of glomerular endothelia. J Am Soc Nephrol 18:2320–2329PubMedCrossRef Davis B, Dei Cas A, Long DA, White KE, Hayward A, Ku CH, Woolf AS, Bilous R, Viberti G, Gnudi L (2007) Podocyte-specific expression of angiopoietin-2 causes proteinuria and apoptosis of glomerular endothelia. J Am Soc Nephrol 18:2320–2329PubMedCrossRef
51.
go back to reference Yuan HT, Tipping PG, Li XZ, Long DA, Woolf AS (2002) Angiopoietin correlates with glomerular capillary loss in anti-glomerular basement membrane glomerulonephritis. Kidney Int 61:2078–2089PubMedCrossRef Yuan HT, Tipping PG, Li XZ, Long DA, Woolf AS (2002) Angiopoietin correlates with glomerular capillary loss in anti-glomerular basement membrane glomerulonephritis. Kidney Int 61:2078–2089PubMedCrossRef
Metadata
Title
Soluble VEGF receptor 1 promotes endothelial injury in children and adolescents with lupus nephritis
Authors
Monika Edelbauer
Sudhir Kshirsagar
Magdalena Riedl
Heiko Billing
Burkhard Tönshoff
Dieter Haffner
Jörg Dötsch
Gottfried Wechselberger
Lutz T. Weber
Elisabeth Steichen-Gersdorf
Publication date
01-05-2012
Publisher
Springer-Verlag
Published in
Pediatric Nephrology / Issue 5/2012
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-011-2062-z

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