The therapeutic potential of VEGF inhibition in diabetic microvascular complications

Am J Cardiovasc Drugs. 2007;7(6):393-8. doi: 10.2165/00129784-200707060-00002.

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.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / etiology
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / etiology
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / etiology
  • Humans
  • Neovascularization, Pathologic / drug therapy
  • Vascular Endothelial Growth Factors / antagonists & inhibitors*

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factors