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Journal of Diabetes Research
Volume 2013, Article ID 184539, 7 pages
Review Article

Uncoupling of VEGF with Endothelial NO as a Potential Mechanism for Abnormal Angiogenesis in the Diabetic Nephropathy

1TMK Project, Kyoto University Graduate School of Medicine, Kyoto 606-8397, Japan
2Department of Nephrology, Nagoya University Graduate School of Medicine, 466-8550, Japan
3Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO 80045, USA

Received 26 September 2013; Accepted 7 November 2013

Academic Editor: Keizo Kanasaki

Copyright © 2013 Takahiko Nakagawa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.