Department of Neurology, Klinikum Bremen-Ost, Bremen, Germany.
Neuromuscul Disord. 2010 Mar;20(3):192-7. doi: 10.1016/j.nmd.2010.01.005. Epub 2010 Feb 1.
Dermatomyositis and vasculitic neuropathies are disorders with immune mediated ischemic injuries. Cellular responses to hypoxia include the hypoxia-inducible factor-1 (HIF-1)-induced transcription of genes involved in angiogenesis. To study their possible roles in those disorders, the immunohistochemical expression of HIF-1alpha, HIF-1beta, HIF-2alpha, vascular endothelial growth factor (VEGF), VEGF-receptor (VEGF-R) and erythropoietin-receptor was investigated. Cases of normal nerves, diabetic neuropathy, normal muscles, polymyositis and inclusion-body-myositis served as controls. The latter were chosen because they represent comparable inflammatory disorders, however, in these ischemia/hypoxia is not supposed to play such a prominent pathogenetic role. Hypoxia-related proteins were not detected in normal controls. In polymyositis and inclusion-body-myositis, there was VEGF-R-expression in muscle fibers and HIF-2alpha reactivity in endothelial cells. In dermatomyositis, HIF-1alpha and HIF-1beta were found in endothelial cells, whereas HIF-2alpha, erythropoietin-receptor, VEGF and VEGF-R additionally were observed in muscle fibers. In vasculitic and diabetic neuropathies, a variable focal expression of hypoxia-inducible factors, VEGF, VEGF-R and erythropoietin-receptor was seen in vessels. These observations suggest that the upregulation of hypoxia-related proteins may represent an adaptation mechanism of neuromuscular tissues to immune mediated deprivation of the blood supply.
皮肌炎和血管炎性神经病是具有免疫介导性缺血损伤的疾病。细胞对缺氧的反应包括缺氧诱导因子-1（HIF-1）诱导参与血管生成的基因的转录。为了研究它们在这些疾病中的可能作用，研究了 HIF-1alpha、HIF-1beta、HIF-2alpha、血管内皮生长因子（VEGF）、VEGF 受体（VEGF-R）和促红细胞生成素受体的免疫组化表达。正常神经、糖尿病性神经病、正常肌肉、多发性肌炎和包涵体肌炎的病例作为对照。选择后者是因为它们代表了可比的炎症性疾病，然而，在这些疾病中，缺血/缺氧不应发挥如此突出的致病作用。正常对照中未检测到与缺氧相关的蛋白。在多发性肌炎和包涵体肌炎中，肌纤维中存在 VEGF-R 表达，内皮细胞中存在 HIF-2alpha 反应性。在皮肌炎中，内皮细胞中存在 HIF-1alpha 和 HIF-1beta，而肌肉纤维中还观察到 HIF-2alpha、促红细胞生成素受体、VEGF 和 VEGF-R。在血管炎性和糖尿病性神经病中，血管中可见缺氧诱导因子、VEGF、VEGF-R 和促红细胞生成素受体的可变局灶性表达。这些观察结果表明，缺氧相关蛋白的上调可能代表神经肌肉组织对免疫介导的血液供应剥夺的适应机制。
