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

Rheumatol Int. 2004 Nov;24(6):333-9. doi: 10.1007/s00296-003-0379-z. Epub 2003 Sep 12.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / analysis
  • Biopsy, Needle
  • Case-Control Studies
  • DNA-Binding Proteins / metabolism*
  • Dermatomyositis / pathology
  • 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*

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Integrin alpha Chains
  • Integrin beta Chains
  • Nuclear Proteins
  • Transcription Factors
  • Vascular Endothelial Growth Factor Receptor-1