TY - JOUR
T1 - Vascular endothelial growth factor accelerates renal recovery in experimental thrombotic microangiopathy
AU - Kim, Yoon Goo
AU - Suga, Shin Ichi
AU - Kang, Duk Hee
AU - Jeffferson, J. Ashley
AU - Mazzali, Marilda
AU - Gordon, Katherine L.
AU - Matsui, Katsuyuki
AU - Breiteneder-Geleff, Silvana
AU - Shankland, Stuart J.
AU - Hughes, Jeremy
AU - Kerjaschki, Dontscho
AU - Schreiner, George F.
AU - Johnson, Richard J.
N1 - Funding Information:
Y-G. Kim is a recipient of the International Fellowship Award of the International Society of Nephrology. Additional support was from U.S. Public Health grants DK-52121, DK-43422, and DK-47695 and a small grant from SCIOS (Sunnyvale, CA, USA), Samsung Biomedical Research Institute (C-A0-018-1), and Samsung Medical Center.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Endothelium
KW - Hemolytic uremic syndrome
KW - Ischemia
UR - http://www.scopus.com/inward/record.url?scp=0033667542&partnerID=8YFLogxK
U2 - 10.1046/j.1523-1755.2000.00422.x
DO - 10.1046/j.1523-1755.2000.00422.x
M3 - Article
C2 - 11115072
AN - SCOPUS:0033667542
VL - 58
SP - 2390
EP - 2399
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 6
ER -