Xia Yu-Ping, Li Baosheng, Hylton Donna, Detmar Michael, Yancopoulos George D, Rudge John S
Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Blood. 2003 Jul 1;102(1):161-8. doi: 10.1182/blood-2002-12-3793. Epub 2003 Mar 20.
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.
涉及血管内皮生长因子（VEGF）以促进治疗性血管生成的基因治疗方法正在被考虑用于从缺血性心脏病到不愈合皮肤溃疡等多种病症。在此，我们有一个惊人的发现，即向皮肤转基因递送VEGF会导致一种严重的炎症性皮肤病，具有许多银屑病的细胞和分子特征，包括特征性的血管变化、表皮改变和炎症浸润。在这个模型中，即使是长期的银屑病也仍然依赖转基因VEGF，因为添加强效VEGF拮抗剂VEGF Trap可以有效逆转这种疾病。以前通过转基因递送表皮角质形成细胞生长因子或炎症介质来忠实地复制银屑病表型的尝试所产生的表型与人类银屑病只有部分相似，这使得关于这种疾病病因的问题仍未得到解答。转基因VEGF诱导银屑病样表型的能力为这种疾病提示了一种新的病因和治疗方法，并进一步证实了人们对递送VEGF的治疗尝试可能会产生的促炎不良反应的新担忧。
