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Disease-associated increased HIF-1, αvβ3 integrin, and Flt-1 do not suffice to compensate the damage-inducing loss of blood vessels in inflammatory myopathies

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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-1β (HIF-1β), β3 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-1β, β3, 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.

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Fig. 1A–F.
Fig. 2A–F.

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Acknowledgements

This study was supported by the Academy of Finland, TEKES, University of Helsinki, Sigrid Juselius Foundation, and Finska Läkaresällskapet. We would like to acknowledge the skillful technical assistance by bioanalyst Eija Kaila and the secretarial work by Outi Rauanheimo.

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Authors and Affiliations

  1. Department of Medicine/Invärtes medicin, Biomedicum, P.O. Box 700, 00029 Helsinki University Central Hospital, Helsinki, Finland

    Yrjö T. Konttinen

  2. Department of Anatomy, Institute of Biomedicine, Helsinki University, Helsinki, Finland

    Yrjö T. Konttinen, Zygmunt Mackiewicz, Mika Hukkanen & Ismo Virtanen

  3. Orton Research Institute and the Orthopaedic Hospital of the Invalid Foundation, Helsinki, Finland

    Yrjö T. Konttinen

  4. Vilnius University Institute of Experimental and Clinical Medicine, Vilnius, Lithuania

    Zygmunt Mackiewicz & Danutė Povilėnaitė

  5. Department of Veterinary Pathology, University of Helsinki, Helsinki, Finland

    Antti Sukura

  6. Department of Cell Biology, University of Opole, Poland

    Zygmunt Mackiewicz

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  1. Yrjö T. Konttinen
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  2. Zygmunt Mackiewicz
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  3. Danutė Povilėnaitė
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Correspondence to Yrjö T. Konttinen.

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Konttinen, Y.T., Mackiewicz, Z., Povilėnaitė, D. et al. Disease-associated increased HIF-1, αvβ3 integrin, and Flt-1 do not suffice to compensate the damage-inducing loss of blood vessels in inflammatory myopathies. Rheumatol Int 24, 333–339 (2004). https://doi.org/10.1007/s00296-003-0379-z

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  • DOI: https://doi.org/10.1007/s00296-003-0379-z

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