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Disease-associated increased HIF-1, alphavbeta3 integrin, and Flt-1 do not suffice to compensate the damage-inducing loss of blood vessels in inflammatory myopathies
by
Konttinen, Yrjö T.
, Povilėnaitė, Danutė
, Hukkanen, Mika
, Virtanen, Ismo
, Sukura, Antti
, Mackiewicz, Zygmunt
in
Biomarkers - analysis
/ Biopsy, Needle
/ Case-Control Studies
/ Dermatomyositis - pathology
/ DNA-Binding Proteins - metabolism
/ Female
/ Humans
/ Hypoxia-Inducible Factor 1
/ Hypoxia-Inducible Factor 1, alpha Subunit
/ Immunohistochemistry
/ Integrin alpha Chains - metabolism
/ Integrin beta Chains - metabolism
/ Lupus Erythematosus, Systemic - pathology
/ Male
/ Muscular Diseases - pathology
/ Nuclear Proteins - metabolism
/ Polymyositis - pathology
/ Prognosis
/ Scleroderma, Systemic - pathology
/ Sensitivity and Specificity
/ Tissue Culture Techniques
/ Transcription Factors - metabolism
/ Vascular Endothelial Growth Factor Receptor-1 - metabolism
2004
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Disease-associated increased HIF-1, alphavbeta3 integrin, and Flt-1 do not suffice to compensate the damage-inducing loss of blood vessels in inflammatory myopathies
by
Konttinen, Yrjö T.
, Povilėnaitė, Danutė
, Hukkanen, Mika
, Virtanen, Ismo
, Sukura, Antti
, Mackiewicz, Zygmunt
in
Biomarkers - analysis
/ Biopsy, Needle
/ Case-Control Studies
/ Dermatomyositis - pathology
/ DNA-Binding Proteins - metabolism
/ Female
/ Humans
/ Hypoxia-Inducible Factor 1
/ Hypoxia-Inducible Factor 1, alpha Subunit
/ Immunohistochemistry
/ Integrin alpha Chains - metabolism
/ Integrin beta Chains - metabolism
/ Lupus Erythematosus, Systemic - pathology
/ Male
/ Muscular Diseases - pathology
/ Nuclear Proteins - metabolism
/ Polymyositis - pathology
/ Prognosis
/ Scleroderma, Systemic - pathology
/ Sensitivity and Specificity
/ Tissue Culture Techniques
/ Transcription Factors - metabolism
/ Vascular Endothelial Growth Factor Receptor-1 - metabolism
2004
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Disease-associated increased HIF-1, alphavbeta3 integrin, and Flt-1 do not suffice to compensate the damage-inducing loss of blood vessels in inflammatory myopathies
by
Konttinen, Yrjö T.
, Povilėnaitė, Danutė
, Hukkanen, Mika
, Virtanen, Ismo
, Sukura, Antti
, Mackiewicz, Zygmunt
in
Biomarkers - analysis
/ Biopsy, Needle
/ Case-Control Studies
/ Dermatomyositis - pathology
/ DNA-Binding Proteins - metabolism
/ Female
/ Humans
/ Hypoxia-Inducible Factor 1
/ Hypoxia-Inducible Factor 1, alpha Subunit
/ Immunohistochemistry
/ Integrin alpha Chains - metabolism
/ Integrin beta Chains - metabolism
/ Lupus Erythematosus, Systemic - pathology
/ Male
/ Muscular Diseases - pathology
/ Nuclear Proteins - metabolism
/ Polymyositis - pathology
/ Prognosis
/ Scleroderma, Systemic - pathology
/ Sensitivity and Specificity
/ Tissue Culture Techniques
/ Transcription Factors - metabolism
/ Vascular Endothelial Growth Factor Receptor-1 - metabolism
2004
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Disease-associated increased HIF-1, alphavbeta3 integrin, and Flt-1 do not suffice to compensate the damage-inducing loss of blood vessels in inflammatory myopathies
Journal Article
Disease-associated increased HIF-1, alphavbeta3 integrin, and Flt-1 do not suffice to compensate the damage-inducing loss of blood vessels in inflammatory myopathies
2004
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Overview
To analyze the microvascular network in skeletal muscle biopsies from patients with dermatomyositis (DM) and systemic sclerosis (SSc) compared to polymyositis (PM) and systemic lupus erythematosus (SLE), and non-inflammatory myopathies, and to clarify whether reparative angiogenesis-related factors are expressed in parallel to blood vessel damage.
Immunohistochemical staining of muscle biopsies (10 DM, 10 SSc, 10 PM, 10 SLE, and 10 non-inflammatory myopathies) with antibodies against von Willebrand factor (vWF), hypoxia-inducible factor-1beta (HIF-1beta), beta3 integrin subunit, and vascular endothelial growth factor receptor-1 (VEGFR-1). The TechMate staining robot and biotin-streptavidin protocol were used.
DM and SSc muscles were characterized by endothelial damage and reduction of blood vessel network. Expression of angiogenesis-related factors (HIF-1beta, beta3, VEGFR-1) was also found in the same biopsies. In contrast, in PM and SLE muscles, vascular networks were apparently not affected and angiogenic stimuli were less expressed if at all.
This work demonstrates that in inflamed muscles hypoxia/ischemia induces increased expression of angiogenic factors, yet their impact is insufficient to repair disease-associated reduction of the capillary network. This leads to questions considering the usefulness of angiogenic factors in the treatment of ischemic inflammatory myopathies in DM and SSc.
Subject
/ DNA-Binding Proteins - metabolism
/ Female
/ Humans
/ Hypoxia-Inducible Factor 1, alpha Subunit
/ Integrin alpha Chains - metabolism
/ Integrin beta Chains - metabolism
/ Lupus Erythematosus, Systemic - pathology
/ Male
/ Muscular Diseases - pathology
/ Nuclear Proteins - metabolism
/ Scleroderma, Systemic - pathology
/ Transcription Factors - metabolism
/ Vascular Endothelial Growth Factor Receptor-1 - metabolism
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