Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis.
Gene therapy approaches involving vascular endothelial growth factor (VEGF) to promote therapeutic angiogenesis are under consideration for conditions ranging from ischemic heart disease to nonhealing skin ulcers. Here we make the surprising observation that the 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 longstanding psoriatic disease remains dependent on the transgenic VEGF in this model because it can be effectively reversed by the addition of VEGF Trap, a potent VEGF antagonist. Previous attempts to faithfully replicate the psoriatic phenotype through the transgenic delivery of epidermal keratinocyte growth factors or inflammatory mediators generated phenotypes with only partial resemblance to human psoriasis, leaving unanswered questions about the etiology of this disease. The ability of transgenic VEGF to induce a psoriasiform phenotype suggests a new etiology and treatment approach for this disease and further substantiates emerging concerns about possible proinflammatory adverse effects that might be associated with therapeutic attempts to deliver VEGF.
Xia
Yu-Ping
YP
Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. yuping.xia@regeneron.com
Li
Baosheng
B
Hylton
Donna
D
Detmar
Michael
M
Yancopoulos
George D
GD
Rudge
John S
JS
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000009:adverse effects*; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000209:etiology; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000009:adverse effects*; D008222:Lymphokines / Q000008:administration & dosage* / Q000009:adverse effects*; D051379:Mice; D008822:Mice, Transgenic; D011565:Psoriasis / Q000139:chemically induced* / Q000209:etiology; D017978:Receptors, Growth Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D019076:Transgenes; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D017978:Receptors, Growth Factor; D011993:Recombinant Fusion Proteins; C460365:VEGF Trap R1R2 protein; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors