Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes

A. S. De Vriese, Ronald Tilton, M. Elger, C. C. Stephan, W. Kriz, N. H. Lameire

Research output: Contribution to journalArticle

389 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) is a cytokine that potently stimulates angiogenesis, microvascular hyperpermeability, and endothelium-dependent vasodilation, effects that are largely mediated by endothelial nitric oxide synthase (eNOS). The expression of VEGF is pronounced in glomerular visceral epithelial cells, but its function in renal physiology and pathophysiology is unknown. VEGF expression is upregulated by high ambient glucose concentrations in several cell types in vitro and in glomeruli of diabetic rats. To assess the role of VEGF in the pathophysiology of early renal dysfunction in diabetes, monoclonal anti-VEGF antibodies (Ab) were administered to control and streptozotocin-induced diabetic rats for 6 wk after induction of diabetes. Based on in vitro binding studies, an adequate serum VEGF inhibitory activity was achieved during the entire course of anti-VEGF Ab administration. Anti-VEGF Ab treatment but not administration of isotype-matched control Ab decreased hyperfiltration, albuminuria, and glomerular hypertrophy in diabetic rats. VEGF blockade also prevented the upregulation of eNOS expression in glomerular capillary endothelial cells of diabetic rats. Antagonism of VEGF had no effect on GFR and glomerular volume in control rats. These results identify VEGF as a pathogenetic link between hyperglycemia and early renal dysfunction in diabetes. Targeting VEGF may prove useful as a therapeutic strategy for the treatment of early diabetic nephropathy.

Original languageEnglish (US)
Pages (from-to)993-1000
Number of pages8
JournalJournal of the American Society of Nephrology
Volume12
Issue number5
StatePublished - 2001
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor A
Kidney
Antibodies
Nitric Oxide Synthase Type III
Podocytes
Albuminuria
Diabetic Nephropathies
Streptozocin
Vasodilation
Hyperglycemia
Hypertrophy
Endothelium
Up-Regulation
Endothelial Cells
Cytokines
Glucose

ASJC Scopus subject areas

  • Nephrology

Cite this

De Vriese, A. S., Tilton, R., Elger, M., Stephan, C. C., Kriz, W., & Lameire, N. H. (2001). Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. Journal of the American Society of Nephrology, 12(5), 993-1000.

Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. / De Vriese, A. S.; Tilton, Ronald; Elger, M.; Stephan, C. C.; Kriz, W.; Lameire, N. H.

In: Journal of the American Society of Nephrology, Vol. 12, No. 5, 2001, p. 993-1000.

Research output: Contribution to journalArticle

De Vriese, AS, Tilton, R, Elger, M, Stephan, CC, Kriz, W & Lameire, NH 2001, 'Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes', Journal of the American Society of Nephrology, vol. 12, no. 5, pp. 993-1000.
De Vriese, A. S. ; Tilton, Ronald ; Elger, M. ; Stephan, C. C. ; Kriz, W. ; Lameire, N. H. / Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. In: Journal of the American Society of Nephrology. 2001 ; Vol. 12, No. 5. pp. 993-1000.
@article{8867413fbe2a43df81f367e700ad6b2e,
title = "Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes",
abstract = "Vascular endothelial growth factor (VEGF) is a cytokine that potently stimulates angiogenesis, microvascular hyperpermeability, and endothelium-dependent vasodilation, effects that are largely mediated by endothelial nitric oxide synthase (eNOS). The expression of VEGF is pronounced in glomerular visceral epithelial cells, but its function in renal physiology and pathophysiology is unknown. VEGF expression is upregulated by high ambient glucose concentrations in several cell types in vitro and in glomeruli of diabetic rats. To assess the role of VEGF in the pathophysiology of early renal dysfunction in diabetes, monoclonal anti-VEGF antibodies (Ab) were administered to control and streptozotocin-induced diabetic rats for 6 wk after induction of diabetes. Based on in vitro binding studies, an adequate serum VEGF inhibitory activity was achieved during the entire course of anti-VEGF Ab administration. Anti-VEGF Ab treatment but not administration of isotype-matched control Ab decreased hyperfiltration, albuminuria, and glomerular hypertrophy in diabetic rats. VEGF blockade also prevented the upregulation of eNOS expression in glomerular capillary endothelial cells of diabetic rats. Antagonism of VEGF had no effect on GFR and glomerular volume in control rats. These results identify VEGF as a pathogenetic link between hyperglycemia and early renal dysfunction in diabetes. Targeting VEGF may prove useful as a therapeutic strategy for the treatment of early diabetic nephropathy.",
author = "{De Vriese}, {A. S.} and Ronald Tilton and M. Elger and Stephan, {C. C.} and W. Kriz and Lameire, {N. H.}",
year = "2001",
language = "English (US)",
volume = "12",
pages = "993--1000",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "5",

}

TY - JOUR

T1 - Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes

AU - De Vriese, A. S.

AU - Tilton, Ronald

AU - Elger, M.

AU - Stephan, C. C.

AU - Kriz, W.

AU - Lameire, N. H.

PY - 2001

Y1 - 2001

N2 - Vascular endothelial growth factor (VEGF) is a cytokine that potently stimulates angiogenesis, microvascular hyperpermeability, and endothelium-dependent vasodilation, effects that are largely mediated by endothelial nitric oxide synthase (eNOS). The expression of VEGF is pronounced in glomerular visceral epithelial cells, but its function in renal physiology and pathophysiology is unknown. VEGF expression is upregulated by high ambient glucose concentrations in several cell types in vitro and in glomeruli of diabetic rats. To assess the role of VEGF in the pathophysiology of early renal dysfunction in diabetes, monoclonal anti-VEGF antibodies (Ab) were administered to control and streptozotocin-induced diabetic rats for 6 wk after induction of diabetes. Based on in vitro binding studies, an adequate serum VEGF inhibitory activity was achieved during the entire course of anti-VEGF Ab administration. Anti-VEGF Ab treatment but not administration of isotype-matched control Ab decreased hyperfiltration, albuminuria, and glomerular hypertrophy in diabetic rats. VEGF blockade also prevented the upregulation of eNOS expression in glomerular capillary endothelial cells of diabetic rats. Antagonism of VEGF had no effect on GFR and glomerular volume in control rats. These results identify VEGF as a pathogenetic link between hyperglycemia and early renal dysfunction in diabetes. Targeting VEGF may prove useful as a therapeutic strategy for the treatment of early diabetic nephropathy.

AB - Vascular endothelial growth factor (VEGF) is a cytokine that potently stimulates angiogenesis, microvascular hyperpermeability, and endothelium-dependent vasodilation, effects that are largely mediated by endothelial nitric oxide synthase (eNOS). The expression of VEGF is pronounced in glomerular visceral epithelial cells, but its function in renal physiology and pathophysiology is unknown. VEGF expression is upregulated by high ambient glucose concentrations in several cell types in vitro and in glomeruli of diabetic rats. To assess the role of VEGF in the pathophysiology of early renal dysfunction in diabetes, monoclonal anti-VEGF antibodies (Ab) were administered to control and streptozotocin-induced diabetic rats for 6 wk after induction of diabetes. Based on in vitro binding studies, an adequate serum VEGF inhibitory activity was achieved during the entire course of anti-VEGF Ab administration. Anti-VEGF Ab treatment but not administration of isotype-matched control Ab decreased hyperfiltration, albuminuria, and glomerular hypertrophy in diabetic rats. VEGF blockade also prevented the upregulation of eNOS expression in glomerular capillary endothelial cells of diabetic rats. Antagonism of VEGF had no effect on GFR and glomerular volume in control rats. These results identify VEGF as a pathogenetic link between hyperglycemia and early renal dysfunction in diabetes. Targeting VEGF may prove useful as a therapeutic strategy for the treatment of early diabetic nephropathy.

UR - http://www.scopus.com/inward/record.url?scp=0035034655&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035034655&partnerID=8YFLogxK

M3 - Article

VL - 12

SP - 993

EP - 1000

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 5

ER -