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Microvascular Loss and Progression of Renal Injury in Renovascular Disease: Renoprotective Effects of VEGF
Author(s) -
Chade Alejandro R.,
Iliescu Radu
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.804.7
Subject(s) - medicine , vascular endothelial growth factor , renal artery stenosis , renal function , urology , fibrosis , kidney disease , angiogenesis , kidney , endocrinology , pathology , renal blood flow , cd31 , renal artery , vegf receptors
Chronic renal artery stenosis (RAS) induces renal functional impairment by promoting microvascular (MV) endothelial dysfunction, damage, and loss, which contributes to the progression of renal injury. Vascular endothelial growth factor (VEGF), crucial for preservation of microvasculature, promotes endothelial repair and modulates renal fibrosis. We hypothesized that administration of VEGF would preserve the renal MV architecture and function during the evolution of RAS. RAS was induced in 12 pigs. VEGF‐165 was intra‐renally infused at the onset of the stenosis (RAS+VEGF, 0.05 ug/kg) in 6 pigs monitored for 6 weeks, and compared to normal controls (n=6). Additional RAS+VEGF pigs underwent revascularization (RV) after 6 weeks, VEGF repeated (RAS+VEGF+RV), and observed for 4 more weeks (n=3). Normal and RAS+RV animals (n=3) served as time‐controls. Single‐kidney hemodynamics and function were assessed in vivo using ultra‐fast CT after 6 and 10 weeks. Renal MV architecture was investigated ex‐vivo using 3D micro‐CT and CD31 immunostaining, and morphology evaluated in cross‐sections stained with trichrome. The degree of RAS and increase in blood pressure were similar in RAS and RAS+VEGF animals. However, decreased RBF, perfusion, and GFR in RAS were normalized in RAS+VEGF and accompanied by augmented renal capillary density and decreased fibrosis. Furthermore, RV normalized GFR and blood pressure only in RAS+VEGF+RV pigs. A single intra‐renal infusion of VEGF improved renal function and decreased fibrosis of the stenotic kidney. This study shows the feasibility of a novel targeted therapeutic approach and supports renoprotective effects of VEGF during the evolution of RAS by preserving renal function not only at the early stage of the disease, but also by improving the responses to revascularization.