Uncoupling of VEGF with endothelial NO as a potential mechanism for abnormal angiogenesis in the diabetic nephropathy.

Abnormal angiogenesis is a well characterized complication in diabetic retinopathy and is now recognized as a feature of diabetic nephropathy. The primary growth factor driving the increased angiogenesis in diabetic retinopathy and nephropathy is vascular endothelial growth factor (VEGF). While VEGF is considered an important growth factor for maintaining glomerular capillary integrity and function, increased action of VEGF in diabetic renal disease may carry adverse consequences. Studies by our group suggest that the effects of VEGF are amplified in the setting of endothelial dysfunction and low nitric oxide (NO) levels, which are a common feature in the diabetic state. The lack of NO may amplify the effects of VEGF to induce inflammation (via effects on the macrophage) and may lead to dysregulation of the vasculature, exacerbating features of diabetic renal disease. In this review, we summarize how an "uncoupling" of the VEGF-NO axis may contribute to the pathology of the diabetic kidney.