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The Therapeutic Potential of VEGF Inhibition in Diabetic Microvascular Complications

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Abstract

During the last few years, the incidence of microvascular complications in diabetes mellitus has rapidly increased as a consequence of both an increase in incidence of type 2 and type 1 diabetes mellitus.

The pathogenesis of diabetic microvascular complications is still largely unknown. Among the many hypotheses, a dysfunction in angiogenesis has been suggested as a common origin for retinopathy, nephropathy, and neuropathy. Based on this hypothesis, inhibition of vascular endothelial growth factor (VEGF) has been tested as a potential therapeutic approach to prevent and cure diabetic microvascular complications. Several VEGF inhibitors are currently under evaluation or are approved for the treatment of wet age-related macular degeneration and macular edema. These include inhibitors of intracellular transcription of VEGF (e.g. bevasiranib), inhibitors of extracellular VEGF (e.g. pegaptanib), inhibitors of VEGF receptor expression (e.g. aflibercept [VEGF-TRAP]) and inhibitors of the intracellular signaling cascade activating VEGF (e.g. midostaurin).

According to the existing evidence base, although inhibition of VEGF results in a better outcome in the case of diabetic retinopathy and also, despite some discrepant results, in the case of diabetic nephropathy, there is no final confirmation that VEGF inhibition is a valid approach for diabetic neuropathy. The latter complication actually, in line with other chronic neuropathies, seems to improve with stimulation of angiogenesis through increased expression of VEGF.

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Acknowledgments

The authors have no conflicts of interest that are directly relevant to the content of this review. No sources of funding were used to assist in the preparation of this review.

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Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, San Raffaele Scientific Institute, Milan, Italy

    Gemma Tremolada & Rosangela Lattanzio

  2. Renal Pathophysiology Unit, San Raffaele Scientific Institute, Milan, Italy

    Gabriella Mazzolari &  Gianpaolo Zerbini

  3. Division of Medicine, San Raffaele Scientific Institute, Via Olgettina, Milan, 60 I — 20132, Italy

    Gianpaolo Zerbini

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  1. Gemma Tremolada
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Correspondence to Gianpaolo Zerbini.

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Tremolada, G., Lattanzio, R., Mazzolari, G. et al. The Therapeutic Potential of VEGF Inhibition in Diabetic Microvascular Complications. Am J Cardiovasc Drugs 7, 393–398 (2007). https://doi.org/10.2165/00129784-200707060-00002

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