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Fibroblast-like synoviocytes from rheumatoid arthritis patients express less flice-inhibitory protein than FLS from osteoarthritis, trauma and prosthesis loosening patie

BioMed Central Ltd.
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  • Biology
  • Medicine


Available online Aetiopathogenesis of rheumatic diseases 1 HIF-1 mediated upregulation of VEGF and VEGF-R in systemic sclerosis (SSc): Imbalance with angiostatic factors suggests VEGF as a novel option for the treatment of ischemia in patients with SSc O Distler*, A Scheid†, A Del Rosso‡, J Rethage*, M Neidhart*, RE Gay*, U Müller-Ladner§, M Gassmann†, M Matucci-Cerinic‡, S Gay* *Ctr Exp Rheum, Zurich, Switzerland †Inst Physiol Univ Zurich, Zurich, Switzerland ‡Dept Med Sect Rheum, Florence, Italy §Dept Int Med I, Univ Hosp, Regensburg, Germany Vascular changes are consistent early findings in patients with SSc and often precede the development of fibrosis. Despite a signifi- cant reduction in the capillary density, there is paradoxically no suf- ficient angiogenesis in the skin of SSc patients. By using a pO2 histograph, we showed that low pO2 values are overt in involved skin of patients with SSc. In vitro, real-time PCR revealed a 3.7-fold upregulation of the potent angiogenic growth factor VEGF in SSc fibroblasts after hypoxic exposure compared to normoxic controls. In situ hybridization for VEGF in skin biopsies of patients with SSc showed an overexpression of VEGF mRNA by fibroblasts and mononuclear infiltrates, whereas its expression was limited to keratinocytes in healthy control biopsies. In contrast to the SSc skin, HIF-1 alpha protein was found to be coexpressed with VEGF in healthy skin samples, indicating that the constitutive VEGF syn- thesis in the skin is driven by this transcription factor. Additionally, we showed that the lack of angiogenesis in SSc is not due to a reduced bioavailability of the overexpressed VEGF, since the VEGF receptors Flk-1 and Flt-1 were found to be expressed on endothelial cells of patients with SSc, but not in healthy controls, and since SSc patients had severely elevated serum levels of VEGF compared to healthy controls. Despite the enhanced levels of VEGF, serum samples of SSc patients did not

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