Document Detail


Microvasculopathic neuromuscular diseases: lessons from hypoxia-inducible factors.
MedLine Citation:
PMID:  20122829     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Stefan Probst-Cousin; Bernhard Neund?rfer; Dieter Heuss
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Publication Detail:
Type:  Journal Article     Date:  2010-02-01
Journal Detail:
Title:  Neuromuscular disorders : NMD     Volume:  20     ISSN:  1873-2364     ISO Abbreviation:  Neuromuscul. Disord.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-17     Completed Date:  2010-06-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111470     Medline TA:  Neuromuscul Disord     Country:  England    
Other Details:
Languages:  eng     Pagination:  192-7     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Neurology, Klinikum Bremen-Ost, Bremen, Germany. stefan.probst@klinikum-bremen-ost.de
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Angiogenesis Inducing Agents / metabolism
Basic Helix-Loop-Helix Transcription Factors / metabolism
Ephrin-B2 / metabolism
Female
Humans
Hypoxia-Inducible Factor 1 / genetics,  metabolism*
Male
Microvessels / metabolism*,  pathology
Middle Aged
Neovascularization, Pathologic / etiology,  metabolism
Neuromuscular Diseases / complications,  metabolism*,  pathology*
Proteins / metabolism
Receptors, Erythropoietin / metabolism
Receptors, Vascular Endothelial Growth Factor / metabolism
Up-Regulation / physiology
Vascular Endothelial Growth Factor A / metabolism
Chemical
Reg. No./Substance:
0/Angiogenesis Inducing Agents; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Ephrin-B2; 0/Hypoxia-Inducible Factor 1; 0/Proteins; 0/Receptors, Erythropoietin; 0/Vascular Endothelial Growth Factor A; 0/endothelial PAS domain-containing protein 1; 0/oxygen-regulated proteins; EC 2.7.10.1/Receptors, Vascular Endothelial Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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