Vascular endothelial growth factor (VEGF121) protects rats from renal infarction in thrombotic microangiopathy

Shin Ichi Suga, Yoon Goo Ki, Alison Joly, Ela Puchacz, Duk Hee Kang, J. Ashley Jefferson, Judith A. Abraham, Jeremy Hughes, Richard J. Johnson, George F. Schreiner

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Background. Renal thrombotic microangiopathy, typified by the hemolytic uremic syndrome, is associated with endothelial cell injury in which the presence of cortical necrosis, extensive glomerular involvement, and arterial occlusive lesions correlates with a poor clinical outcome. We hypothesized that the endothelial survival factor vascular endothelial growth factor (VEGF) may provide protection. Method. Severe, necrotizing, thrombotic microangiopathy was induced in rats by the renal artery perfusion of antiglomerular endothelial antibody, followed by the administration of VEGF or vehicle, and renal injury was evaluated. Results. Control rats developed severe glomerular and tubulointerstitial injury with extensive renal necrosis. The administration of VEGF significantly reduced the necrosis, preserved the glomerular endothelium and arterioles, and reduced the number of apoptotic cells in glomeruli (at 4 hours) and in the tubulointerstitium (at 4 days). The prosurvival effect of VEGF for endothelium may relate in part to the ability of VEGF to protect endothelial cells from factor-induced apoptosis, as demonstrated for tumor necrosis factor-α (TNF-α), which was shown to be up-regulated through the course of this model of renal microangiopathy. Endothelial nitric oxide synthase expression was preserved in VEGF-treated rats compared with its marked decrease in the surviving glomeruli and interstitium of the antibody-treated rats that did not receive VEGF. Conclusions. VEGF protects against renal necrosis in this model of thrombotic microangiopathy. This protection may be mediated by maintaining endothelial nitric oxide production and/or preventing endothelial cell death.

Original languageEnglish
Pages (from-to)1297-1308
Number of pages12
JournalKidney International
Issue number4
StatePublished - 2001

Bibliographical note

Funding Information:
Support for this study was provided by United States Public Health Science grants DK-52121, HL-68607, DK-47659 and a small grant from Scios Inc. Dr. Shin-ichi Suga was supported by Banyu Fellowships Awards in Lipid Metabolism and Atherosclerosis, which are sponsored by Banyu Pharmaceutical Co., Ltd., and the Merck Company Foundation, and Uehara Memorial Foundation Research Fellowship. Dr. Ashley Jefferson was supported by a fellowship grant from the National Kidney Foundation.


  • Apoptosis
  • Arterial occlusive lesions
  • Hemolytic uremic syndrome
  • Nitric oxide synthase
  • Renal injury
  • Tumor necrosis factor-α


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