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

Kidney Int. 2001 Oct;60(4):1297-308. doi: 10.1046/j.1523-1755.2001.00935.x.


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-alpha (TNF-alpha), 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood Vessels / drug effects
  • Blood Vessels / pathology
  • Endothelial Growth Factors / therapeutic use*
  • Hemolytic-Uremic Syndrome / drug therapy
  • Hemolytic-Uremic Syndrome / pathology
  • Infarction / prevention & control*
  • Kidney / drug effects
  • Kidney / enzymology
  • Kidney / pathology
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / pathology
  • Lymphokines / therapeutic use*
  • Male
  • Microcirculation
  • Necrosis
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type III
  • Rats
  • Rats, Sprague-Dawley
  • Renal Circulation*
  • Thrombosis / drug therapy*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Lymphokines
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat