Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis

• Published in: Blood 2003-07, Vol.102 (1), p.161-168
• Main Authors: Xia, Yu-Ping, Li, Baosheng, Hylton, Donna, Detmar, Michael, Yancopoulos, George D., Rudge, John S.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood Vessels - drug effects; Blood Vessels - pathology; Dermatology; Disease Models, Animal; Endothelial Growth Factors - administration & dosage; Endothelial Growth Factors - adverse effects; Genetic Therapy - adverse effects; Genetic Therapy - methods; Humans; Immunohistochemistry; Inflammation - chemically induced; Inflammation - etiology; Intercellular Signaling Peptides and Proteins - administration & dosage; Intercellular Signaling Peptides and Proteins - adverse effects; Lymphokines - administration & dosage; Lymphokines - adverse effects; Medical sciences; Mice; Mice, Transgenic; Psoriasis - chemically induced; Psoriasis - etiology; Psoriasis. Parapsoriasis. Lichen; Receptors, Growth Factor; Recombinant Fusion Proteins - pharmacology; Skin - drug effects; Skin - injuries; Skin - pathology; Transgenes; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-12-3793

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. (Blood. 2003;102:161-168)