Vascular endothelial growth factor expression and glomerular endothelial cell loss in the remnant kidney model.
BACKGROUND
Vascular endothelial growth factor (VEGF) is constitutively expressed in the glomerulus where it may have a role in the maintenance of capillary endothelial cell integrity. The present study sought to examine changes in VEGF expression in a model of progressive renal disease and to assess the effects of angiotensin converting enzyme (ACE) inhibition.


METHODS
Subtotal nephrectomized (STNx) rats were randomly assigned to receive vehicle (n=10) or the ACE inhibitor perindopril (8 mg/l drinking water) for 12 weeks duration (n=10). Sham-operated rats were used as controls (n=10). Glomerular capillary endothelial cell density was evaluated by immunostaining for the pan-endothelial cell marker RECA-1 and VEGF expression was assessed by quantitative in situ hybridization.


RESULTS
In STNx rats glomerular capillary endothelial cell density was reduced to 19% that of sham rats (P<0.01) with a concomitant reduction in glomerular VEGF expression, also to 19% of sham rats (P<0.01). Perindopril treatment was associated with normalization of both capillary endothelial cell density and glomerular VEGF mRNA.


CONCLUSIONS
Reduction in glomerular VEGF expression is a feature of the renal pathology that follows subtotal nephrectomy. In the context of the known functions of this growth factor, these findings suggest that diminution in VEGF may contribute to the demonstrated loss of glomerular endothelium that develops in this model of progressive renal disease.
Kelly
Darren J
DJ
Department of Medicine, University of Melbourne, St Vincent's Hospital, Fitzroy, Australia. dkelly@medstv.unimelb.edu.au
Hepper
Claire
C
Wu
Leonard L
LL
Cox
Alison J
AJ
Gilbert
Richard E
RE
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000235:genetics*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics*; D017403:In Situ Hybridization; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000187:drug effects* / Q000473:pathology; D008297:Male; D020913:Perindopril / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000187:drug effects / Q000235:genetics*
D000806:Angiotensin-Converting Enzyme Inhibitors; D016228:Endothelial Growth Factors; D042461:Vascular Endothelial Growth Factor A; D020913:Perindopril