Reduced vascular endothelial growth factor expression and intra-epidermal nerve fiber loss in human diabetic neuropathy
Reduced vascular endothelial growth factor expression and intra-epidermal nerve fiber loss in human diabetic neuropathy
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DOI：
10.2337/dc07-1556
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发表时间：
2008-01-01
期刊：
影响因子：
16.2
通讯作者：
Malik, Rayaz A.
中科院分区：
文献类型：
--
作者：
Quattrini, Cristian;Jeziorska, Maria;Malik, Rayaz A.
目的-为了评估血管内皮生长因子（VEGF）在维持糖尿病神经病变周围神经完整性中的相关性，我们评估了糖尿病患者皮肤活检样本中VEGF和表皮内神经纤维密度（IENFD）的表达。和自主神经功能测试用激光多普勒血流仪评价皮肤血流反应。在足背进行皮肤活检，并定量IENFD，并与血管内皮生长因子A（VEGF-A），其受体血管内皮生长因子受体2（VEGFR-2），缺氧诱导因子1 α（HIF-1 α）和微血管密度的表达进行比较。结果- IENFD随着糖尿病神经病变严重程度的增加而进行性降低（P < 0.001）。糖尿病合并轻、中度神经病变患者真皮对乙酰胆碱的血流反应性降低（P < 0.01），表皮VEGF-A染色强度明显低于对照组（P < 0.01）。表皮HIF-1 α和VEGFR-2的表达并没有不同groups.CONCLUSIONS进行性内皮功能障碍，减少VEGF的表达，和损失的表皮内神经纤维发生在糖尿病患者的足部皮肤神经病变的严重程度增加。
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 la (HIF-l alpha), 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-la 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.