| Autor: |
Zibert JR; Department of Dermato-Allergology, University of Copenhagen, Gentofte Hospital, Hellerup, Denmark., Wallbrecht K, Schön M, Mir LM, Jacobsen GK, Trochon-Joseph V, Bouquet C, Villadsen LS, Cadossi R, Skov L, Schön MP |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of clinical investigation [J Clin Invest] 2011 Jan; Vol. 121 (1), pp. 410-21. Date of Electronic Publication: 2010 Dec 06. |
| DOI: |
10.1172/JCI41295 |
| Abstrakt: |
Dysregulated angiogenesis is a hallmark of chronic inflammatory diseases, including psoriasis, a common skin disorder that affects approximately 2% of the population. Studying both human psoriasis in 2 complementary xenotransplantation models and psoriasis-like skin lesions in transgenic mice with epidermal expression of human TGF-β1, we have demonstrated that antiangiogenic non-viral somatic gene therapy reduces the cutaneous microvasculature and alleviates chronic inflammatory skin disorders. Transient muscular expression of the recombinant disintegrin domain (RDD) of metargidin (also known as ADAM-15) by in vivo electroporation reduced cutaneous angiogenesis and vascularization in all 3 models. As demonstrated using red fluorescent protein-coupled RDD, the treatment resulted in muscular expression of the gene product and its deposition within the cutaneous hyperangiogenic connective tissue. High-resolution ultrasound revealed reduced cutaneous blood flow in vivo after electroporation with RDD but not with control plasmids. In addition, angiogenesis- and inflammation-related molecular markers, keratinocyte proliferation, epidermal thickness, and clinical disease scores were downregulated in all models. Thus, non-viral antiangiogenic gene therapy can alleviate psoriasis and may do so in other angiogenesis-related inflammatory skin disorders. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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