Impaired angiogenesis in the remnant kidney model: II. Vascular endothelial growth factor administration reduces renal fibrosis and stabilizes renal function.

Abstract

Impaired angiogenesis and decreased vascular endothelial growth factor (VEGF) expression were recently documented in the remnant kidney (RK) model of progressive renal failure. VEGF (50 microg/kg, twice daily) was administered to RK rats between weeks 4 and 8 after surgery, and rats were euthanized at week 8 for histologic study. During the administration of VEGF (n = 7) or vehicle (n = 6), systemic BP was comparable in the two groups. VEGF treatment resulted in improved renal function and lower mortality rates, compared with the vehicle-treated group. Renal histologic analyses confirmed a 3.5-fold increase in glomerular endothelial cell proliferation (0.14 +/- 0.03 versus 0.04 +/- 0.02 proliferating endothelial cells/glomerulus, VEGF versus vehicle, P < 0.05), a twofold increase in peritubular capillary endothelial cell proliferation (1.60 +/- 0.30 versus 0.78 +/- 0.17 cells/mm(2), VEGF versus vehicle, P < 0.01), a threefold decrease in peritubular capillary rarefaction (P < 0.01), and a twofold increase in endothelial nitrix oxide synthase expression (P < 0.05) in the VEGF-treated group; an eightfold increase in urinary nitrate/nitrite levels (P < 0.05) was also noted. Although the difference in glomerulosclerosis scores did not reach statistical significance (0.67 +/- 0.42 versus 1.22 +/- 0.63, VEGF versus vehicle; range, 0 to 4; P = NS), VEGF-treated rats exhibited less interstitial collagen type III deposition (9.32 +/- 3.26 versus 17.45 +/- 7.50%, VEGF versus vehicle, P < 0.01) and reduced tubular epithelial cell injury, as manifested by osteopontin expression (5.57 +/- 1.60 versus 9.58 +/- 3.45%, VEGF versus vehicle, P < 0.01). In conclusion, VEGF treatment reduces fibrosis and stabilizes renal function in the RK model. The use of angiogenic factors may represent a new approach to the treatment of kidney disease.

• Authors: Duk-Hee Kang, Jeremy Hughes, Marilda Mazzali, George F Schreiner, Richard J Johnson
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 12 Issue 7 Pg. 1448-1457 (Jul 2001) ISSN: 1046-6673 [Print] United States
• PMID: 11423573 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Endothelial Growth Factors
• Lymphokines
• Nitrites
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors
• Nitric Oxide Synthase

Topics

• Animals
• Blood Pressure (drug effects)
• Capillaries (drug effects, pathology)
• Endothelial Growth Factors (pharmacology)
• Fibrosis
• Glomerulosclerosis, Focal Segmental (pathology)
• Kidney (drug effects, pathology, physiopathology)
• Kidney Diseases (mortality, physiopathology)
• Kidney Glomerulus (blood supply)
• Kidney Tubules (blood supply)
• Lymphokines (pharmacology)
• Macrophages (pathology)
• Male
• Neovascularization, Physiologic
• Nephrectomy
• Nitric Oxide Synthase (metabolism)
• Nitrites (urine)
• Rats
• Rats, Sprague-Dawley
• Renal Circulation (drug effects)
• Time Factors
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors