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Efficient therapy of ischaemic lesions with VEGF121-fibrin in an animal model of systemic sclerosis

Allipour Birgani, Shadab ; Mailänder, Marion ; Wasle, Ines ; Dietrich, Hermann ; Gruber, Johann ; Distler, Oliver ; Sgonc, Roswitha

BMJ Publishing Group 2015-09

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  • Título:
    Efficient therapy of ischaemic lesions with VEGF121-fibrin in an animal model of systemic sclerosis
  • Autor: Allipour Birgani, Shadab ; Mailänder, Marion ; Wasle, Ines ; Dietrich, Hermann ; Gruber, Johann ; Distler, Oliver ; Sgonc, Roswitha
  • Assuntos: Medicine & health ; Rheumatology Clinic and Institute of Physical Medicine
  • Notas: https://www.zora.uzh.ch/id/eprint/114548/
    10.1136/annrheumdis-2015-207548
    Allipour Birgani, Shadab; Mailänder, Marion; Wasle, Ines; Dietrich, Hermann; Gruber, Johann; Distler, Oliver; Sgonc, Roswitha (2015). Efficient therapy of ischaemic lesions with VEGF121-fibrin in an animal model of systemic sclerosis. Annals of the Rheumatic Diseases:1-8.
  • Descrição: BACKGROUND In systemic sclerosis (SSc), chronic and uncontrolled overexpression of vascular endothelial growth factor (VEGF) results in chaotic vessels, and intractable fingertip ulcers. Vice versa, VEGF is a potent mediator of angiogenesis if temporally and spatially controlled. We have addressed this therapeutic dilemma in SSc by a novel approach using a VEGF121 variant that covalently binds to fibrin and gets released on demand by cellular enzymatic activity. Using University of California at Davis (UCD)-206 chickens, we tested the hypothesis that cell-demanded release of fibrin-bound VEGF121 leads to the formation of stable blood vessels, and clinical improvement of ischaemic lesions. METHODS Ninety-one early and late ischaemic comb and neck skin lesions of UCD-206 chickens were treated locally with VEGF121-fibrin, fibrin alone, or left untreated. After 1 week of treatment the clinical outcome was assessed. Angiogenesis was studied by immunofluorescence staining of vascular markers quantitatively analysed using TissueQuest. RESULTS Overall, 79.3% of the lesions treated with VEGF121-fibrin showed clinical improvement, whereas 71.0% of fibrin treated controls, and 93.1% of untreated lesions deteriorated. This was accompanied by significantly increased growth of stable microvessels, upregulation of the proangiogenic VEGFR-2 and its regulator TAL-1, and increase of endogenous endothelial VEGF expression. CONCLUSIONS Our findings in the avian model of SSc suggest that cell-demanded release of VEGF121 from fibrin matrix induces controlled angiogenesis by differential regulation of VEGFR-1 and VEGFR-2 expression, shifting the balance towards the proangiogenic VEGFR-2. The study shows the potential of covalently conjugated VEGF-fibrin matrices for the therapy of ischaemic lesions such as fingertip ulcers.
  • Editor: BMJ Publishing Group
  • Data de criação/publicação: 2015-09
  • Idioma: Inglês;Alemão
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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