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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Curr+Opin+Nephrol+Hypertens
2016 ; 25
(5
): 404-9
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Therapeutic angiogenesis by vascular endothelial growth factor supplementation
for treatment of renal disease
#MMPMID27367910
Logue OC
; McGowan JW
; George EM
; Bidwell GL 3rd
Curr Opin Nephrol Hypertens
2016[Sep]; 25
(5
): 404-9
PMID27367910
show ga
PURPOSE OF REVIEW: Vascular endothelial growth factors (VEGFs) influence renal
function through angiogenesis, with VEGF-A being the most potent inducer of
vascular formation. In the normal glomerulus, tight homeostatic balance is
maintained between the levels of VEGF-A isoforms produced by podocyte cells, and
the VEGF receptors (VEGFRs) expressed by glomerular endothelial, mesangial, and
podocyte cells. Renal disease occurs when this homeostatic balance is lost,
manifesting in the abnormal autocrine and paracrine VEGF-A/VEGFR signaling,
ultrastructural glomerular and tubular damage, and impaired filtration. RECENT
FINDINGS: Preclinical disease models of ischemic renal injury, including acute
ischemia/reperfusion, thrombotic microangiopathy, and chronic renovascular
disease, treated with exogenous VEGF supplementation demonstrated therapeutic
efficacy. These results suggest a therapeutic VEGF-A paracrine effect on
endothelial cells in the context of acute or chronic obstructive ischemia.
Conversely, renal dysfunction in diabetic nephropathy appears to occur through an
upregulated VEGF autocrine effect on podocyte cells, which is exacerbated by
hyperglycemia. Therefore, VEGF supplementation therapy may be contraindicated for
treatment of diabetic nephropathy, but specific results will depend on dose and
on the specific site of VEGF delivery. A drug delivery system that demonstrates
cell specificity for glomerular or peritubular capillaries could be employed to
restore balance to VEGF-A/VEGFR2 signaling, and by doing so, prevent the
progression to end-stage renal disease. SUMMARY: The review discusses the
preclinical data available for VEGF supplementation therapy in models of renal
disease.
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