Antiangiogenic Therapy for Diabetic Nephropathy

Figure 1

Histological alterations of glomeruli associated with excessive (“too much”) or insufficient (“too little”) glomerular vascular endothelial growth factor (VEGF)-A. In conditionally podocyte-specific VEGF-A transgenic mice, VEGF-A-overexpressing glomeruli become hypertrophic with glomerular basement membrane (GBM) thickening and mesangial expansion, similar to early stages of diabetic glomerulopathy [45]. Induction of diabetes in these transgenic mice results in Kimmelstiel-Wilson-like nodular lesions, microaneurysms, and mesangiolysis in the glomeruli [46], which are observed in advanced diabetic nephropathy. In contrast, conditionally podocyte-specific VEGF-A deficient mice show glomerular capillary thrombi and obliterated capillary loops with swollen endothelial cells, consistent with the findings of renal thrombotic microangiopathy [44]. Diabetes accelerates the dropout of glomerular capillaries in this conditional knockout mice, leading to glomerulosclerosis [47].