A new model of renal microvascular endothelial injury.
Although the importance of injury with consequent activation of endothelium is well-recognized in diseases affecting the glomerular endothelial cell (GEN), research on GEN injury in vivo has been hampered by the lack of adequate animal models. Here we report the establishment and characterization of a new GEN injury model in rats. This model was induced by selective renal artery perfusion with anti-GEN IgG and resulted in the severe acute renal failure with marked platelet deposition and development of a thrombotic microangiopathy involving glomeruli. Peritubular capillary endothelial cells were also damaged that was associated with severe tubular necrosis. Although the glomerular changes were severe, half of the glomeruli recovered by day 10, while interstitial changes remained throughout our observation time course. Proliferation of GEN was observed during the recovery phase. An increased expression of endothelial nitric oxide synthase in GEN was also observed, and may be an adaptive mechanism to counteract the thrombosis and ischemia. This model should be useful to investigate the pathophysiology of renal microvascular diseases and the mechanisms of GEN injury, activation and recovery in vivo.
Nangaku
M
M
Division of Nephrology, University of Washington, Seattle, Washington, USA.
Alpers
C E
CE
Pippin
J
J
Shankland
S J
SJ
Adler
S
S
Kurokawa
K
K
Couser
W G
WG
Johnson
R J
RJ
D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology; D000740:Anemia / Q000209:etiology; D000818:Animals; D001806:Blood Urea Nitrogen; D003094:Collagen / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D005337:Fibrin / Q000032:analysis; D007668:Kidney / Q000473:pathology / Q000648:ultrastructure; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007797:Laminin / Q000032:analysis; D008222:Lymphokines / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D013921:Thrombocytopenia / Q000209:etiology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D007797:Laminin; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005337:Fibrin; D003094:Collagen; D003165:Complement System Proteins; D019001:Nitric Oxide Synthase