Reduced VEGF expression and intra-epidermal nerve fiber loss in human diabetic neuropathy

Abstract

OBJECTIVE: To assess the relevance of VEGF in the maintenance of peripheral nerve integrity in diabetic neuropathy we have assessed the expression of VEGF and intraepidermal nerve fibre density (IENFD) in skin biopsies from diabetic patients.

RESEARCH DESIGN AND METHODS: 53 diabetic patients and 12 non-diabetic control subjects underwent neurological evaluation, electrophysiology, quantitative sensory and autonomic function testing. Dermal blood flow responses were evaluated with laser Doppler flowmetry. Skin biopsies were performed on the dorsum of the foot and IENFD was quantified and compared to the expression of VEGF-A, its receptor VEGFR-2, HIF-1α and microvessel density.

RESULTS: IENFD decreased progressively with increasing severity of diabetic neuropathy (P<0.001). Dermal blood flow response to ACh was reduced in diabetic patients with mild and moderate neuropathy (P<0.01) and the intensity of staining for epidermal VEGF-A was significantly reduced in diabetic patients compared to controls (P<0.01). Epidermal HIF-1α and VEGFR-2 expression did not differ between groups

CONCLUSIONS: Progressive endothelial dysfunction, reduction in VEGF expression and loss of intraepidermal nerve fibers occurs in the foot skin of diabetic patients with increasing neuropathic severity.