Blood 2003 Mar 20; [epub ahead of print] Related Articles, Links
Transgenic delivery of VEGF to the mouse skin leads to an inflammatory condition resembling human psoriasis.
Xia YP, Li B, Hylton D, Detmar M, Yancopoulos GD, Rudge JS.
Department of Angiogenesis, Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA.
Gene therapy approaches involving vascular endothelial growth factor (VEGF) to promote therapeutic angiogenesis are being considered for conditions ranging from ischemic heart disease to nonhealing skin ulcers. Here we make the surprising observation that transgenic delivery of VEGF to the skin results in a profound inflammatory skin condition with many of the cellular and molecular features of psoriasis, including the characteristic vascular changes, epidermal alterations and inflammatory infiltrates. Even long-standing psoriatic disease remains dependent on the transgenic VEGF in this model, as it can be effectively reversed by addition of VEGF Trap, a potent VEGF antagonist. Previous attempts to faithfully replicate the psoriatic phenotype via transgenic delivery of epidermal keratinocyte growth factors or inflammatory mediators generated phenotypes with only partial resemblance to the human psoriasis, leaving unanswered questions about the etiology of this disease. The ability of transgenic VEGF to induce a psoriasis-like phenotype suggests a new etiology and treatment approach for this disease, and further substantiates emerging concerns about possible pro-inflammatory adverse effects that might be associated with therapeutic attempts to deliver VEGF. |
