Reduced vascular endothelial growth factor expression and intra-epidermal nerve fiber loss in human diabetic neuropathy

Cristian Quattrini, Maria Jeziorska, Andrew J M Boulton, Rayaz Malik

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE- To assess the relevance of vascular endothelial growth factor (VEGF) in the maintenance of peripheral nerve integrity in diabetic neuropathy we have assessed the expression of VEGF and intra-epidermal nerve fiber density (IENFD) in skin biopsy samples from diabetic patients. RESEARCH DESIGN AND METHODS- Fifty-three diabetic patients and 12 nondiabetic 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 with the expression of vascular endothelial growth factor A (VEGF-A), its receptor vascular endothelial growth factor receptor 2 (VEGFR-2), hypoxia-inducible factor 1α (HIF-1α), and microvessel density. RESULTS- IENFD decreased progressively with increasing severity of diabetic neuropathy (P < 0.001). The dermal blood flow response to acetylcholine 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 with control subjects (P < 0.01). Epidermal HIF-1α and VEGFR-2 expression did not differ between groups. CONCLUSIONS- Progressive endothelial dysfunction, a reduction in VEGF expression, and loss of intra-epidermal nerve fibers occurs in the foot skin of diabetic patients with increasing neuropathic severity.

Original languageEnglish
Pages (from-to)140-145
Number of pages6
JournalDiabetes Care
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 2008
Externally publishedYes

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Diabetic Neuropathies
Nerve Fibers
Vascular Endothelial Growth Factor A
Skin
Hypoxia-Inducible Factor 1
Vascular Endothelial Growth Factor Receptor-2
Biopsy
Laser-Doppler Flowmetry
Diabetic Foot
Electrophysiology
Microvessels
Peripheral Nerves
Acetylcholine
Foot
Research Design
Maintenance
Staining and Labeling

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing

Cite this

Reduced vascular endothelial growth factor expression and intra-epidermal nerve fiber loss in human diabetic neuropathy. / Quattrini, Cristian; Jeziorska, Maria; Boulton, Andrew J M; Malik, Rayaz.

In: Diabetes Care, Vol. 31, No. 1, 01.2008, p. 140-145.

Research output: Contribution to journalArticle

Quattrini, Cristian ; Jeziorska, Maria ; Boulton, Andrew J M ; Malik, Rayaz. / Reduced vascular endothelial growth factor expression and intra-epidermal nerve fiber loss in human diabetic neuropathy. In: Diabetes Care. 2008 ; Vol. 31, No. 1. pp. 140-145.
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