Neuromuscular Disorders
Volume 20, Issue 3 , Pages 192-197, March 2010

Microvasculopathic neuromuscular diseases: Lessons from hypoxia-inducible factors

  • Stefan Probst-Cousin

      Affiliations

    • Department of Neurology, Klinikum Bremen-Ost, Züricher Straße 40, D-28325 Bremen, Germany
    • Corresponding Author InformationCorresponding author. Tel.: +49 421 40861529; fax: +49 421 408 2462.
  • ,
  • Bernhard Neundörfer

      Affiliations

    • Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen, Germany
  • ,
  • Dieter Heuss

      Affiliations

    • Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen, Germany

Received 6 September 2009; received in revised form 21 December 2009; accepted 7 January 2010.

Abstract 

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-1α, HIF-1β, HIF-2α, 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-2α reactivity in endothelial cells. In dermatomyositis, HIF-1α and HIF-1β were found in endothelial cells, whereas HIF-2α, 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.

Keywords: Hypoxia-inducible factors, Vasculitis, Vasculitic neuropathy, Dermatomyositis

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PII: S0960-8966(10)00018-0

doi:10.1016/j.nmd.2010.01.005

Neuromuscular Disorders
Volume 20, Issue 3 , Pages 192-197, March 2010