Vascular endothelial growth factor accelerates renal recovery in experimental thrombotic microangiopathy

Kidney Int. 2000 Dec;58(6):2390-9. doi: 10.1046/j.1523-1755.2000.00422.x.


Background: Renal microvascular injury characterizes thrombotic microangiopathy (TMA). The possibility that angiogenic growth factors may accelerate recovery in TMA has not been studied.

Methods: TMA was induced in rats by the selective right renal artery perfusion of antiglomerular endothelial cell IgG (30 mg/kg). Twenty-four hours later, rats received vascular endothelial growth factor (VEGF121, 100 microg/kg/day) or vehicle (control) daily until day 14. To evaluate renal function, the unperfused left kidney was removed at day 14, and rats were sacrificed at day 17.

Results: The induction of TMA was associated with loss of glomerular and peritubular capillary endothelial cells and decreased arteriolar density at day 1. Some spontaneous capillary recovery was present by day 17; however, repair was incomplete, and severe tubulointerstitial damage occurred. The lack of complete microvascular recovery was associated with reduced VEGF immunostaining in the outer medulla. VEGF-treated rats had more glomeruli with intact endothelium, less glomerular ischemia (collapsed glomeruli), and greater peritubular capillary density with less peritubular capillary loss. This was associated with less tubulointerstitial fibrosis, less cortical atrophy, and improved renal function.

Conclusions: VEGF accelerates renal recovery in this experimental model of TMA. These studies suggest that angiogenic growth factors may provide a new therapeutic strategy for diseases associated with endothelial cell injury.

Publication types

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

MeSH terms

  • Animals
  • Disease Models, Animal
  • Endothelial Growth Factors / pharmacology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology
  • Hemolytic-Uremic Syndrome / drug therapy
  • Hemolytic-Uremic Syndrome / pathology
  • Immunoglobulin G / pharmacology
  • Ischemia / drug therapy*
  • Ischemia / pathology
  • Kidney Glomerulus / blood supply*
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / physiopathology
  • Lymphokines / pharmacology*
  • Male
  • Microcirculation / drug effects
  • Neovascularization, Physiologic / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Thrombosis / drug therapy*
  • Thrombosis / pathology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Immunoglobulin G
  • Lymphokines
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors