Vascular endothelial growth factor accelerates renal recovery in experimental thrombotic microangiopathy

Yoon Goo Kim, Shin Ichi Suga, Duk Hee Kang, J. Ashley Jeffferson, Marilda Mazzali, Katherine L. Gordon, Katsuyuki Matsui, Silvana Breiteneder-Geleff, Stuart J. Shankland, Jeremy Hughes, Dontscho Kerjaschki, George F. Schreiner, Richard J. Johnson

Research output: Contribution to journalArticlepeer-review

200 Scopus citations

Abstract

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 μg/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.

Original languageEnglish
Pages (from-to)2390-2399
Number of pages10
JournalKidney International
Volume58
Issue number6
DOIs
StatePublished - 2000

Keywords

  • Angiogenesis
  • Endothelium
  • Hemolytic uremic syndrome
  • Ischemia

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