The therapeutic potential of VEGF inhibition in diabetic microvascular complications.
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.
Tremolada
Gemma
G
Department of Ophthalmology and Visual Sciences, San Raffaele Scientific Institute, Milan, Italy.
Lattanzio
Rosangela
R
Mazzolari
Gabriella
G
Zerbini
Gianpaolo
G
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000209:etiology; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D042442:Vascular Endothelial Growth Factors