VEGF165 mediates glomerular endothelial repair

VEGF 165 , the most abundant isoform in man, is an angiogenic cytokine that also regulates vascular permeability. Its function in the renal glomerulus, where it is expressed in visceral epithelial and mesangial cells, is unknown. To assess the role of VEGF 165 in glomerular disease, we administered...

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Published in:The Journal of clinical investigation 1999-10, Vol.104 (7), p.913-923
Main Authors: Ostendorf, Tammo, Kunter, Uta, Eitner, Frank, Loos, Anneke, Regele, Heinz, Kerjaschki, Dontscho, Henninger, Dwight D., Janjic, Nebojsa, Floege, Jürgen
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Language:English
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Summary:VEGF 165 , the most abundant isoform in man, is an angiogenic cytokine that also regulates vascular permeability. Its function in the renal glomerulus, where it is expressed in visceral epithelial and mesangial cells, is unknown. To assess the role of VEGF 165 in glomerular disease, we administered a novel antagonist — a high-affinity, nuclease-resistant RNA aptamer coupled to 40-kDa polyethylene glycol (PEG) — to normal rats and to rats with mesangioproliferative nephritis, passive Heymann nephritis (PHN), or puromycin aminonucleoside nephrosis (PAN). In normal rats, antagonism of VEGF 165 for 21 days failed to induce glomerular pathology or proteinuria. In rats with mesangioproliferative nephritis, the VEGF 165 aptamer (but not a sequence-scrambled control RNA or PEG alone) led to a reduction of glomerular endothelial regeneration and an increase in endothelial cell death, provoking an 8-fold increase in the frequency of glomerular microaneurysms by day 6. In contrast, early leukocyte influx and the proliferation, activation, and matrix accumulation of mesangial cells were not affected in these rats. In rats with PHN or PAN, administration of the VEGF 165 aptamer did not influence the course of proteinuria using various dosages and administration routes. These data identify VEGF 165 as a factor of central importance for endothelial cell survival and repair in glomerular disease, and point to a potentially novel way to influence the course of glomerular diseases characterized by endothelial cell damage, such as various glomerulonephritides, thrombotic microangiopathies, or renal transplant rejection.
ISSN:0021-9738
DOI:10.1172/JCI6740