Huggenberger Reto, Detmar Michael
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland.
J Investig Dermatol Symp Proc. 2011 Dec;15(1):24-32. doi: 10.1038/jidsymp.2011.5.
The blood and lymphatic vasculature have an important role in skin homeostasis. Angiogenesis and lymphangiogenesis-the growth of new vessels from existing ones-have received tremendous interest because of their role in promoting cancer spread. However, there is increasing evidence that both vessel types also have a major role in acute and chronic inflammatory disorders. Vessels change their phenotype during inflammation (vascular remodeling). In inflamed skin, vascular remodeling consists of a hyperpermeable, enlarged network of vessels with increased blood flow, and influx of inflammatory cells. During chronic inflammation, the activated endothelium expresses adhesion molecules, cytokines, and other molecules that lead to leukocyte rolling, attachment, and migration into the skin. Recent studies reveal that inhibition of blood vessel activation exerts potent anti-inflammatory properties. Thus, anti-angiogenic drugs might be used to treat inflammatory conditions. In particular, topical application of anti-angiogenic drugs might be ideally suited to circumvent the adverse effects of systemic therapy with angiogenesis inhibitors. Our recent results indicate that stimulation of lymphatic vessel growth and function unexpectedly represents a new approach for treating chronic inflammatory disorders.
血液和淋巴脉管系统在皮肤稳态中发挥着重要作用。血管生成和淋巴管生成(即从现有血管生长出新的血管)因其在促进癌症扩散中的作用而备受关注。然而,越来越多的证据表明,这两种血管类型在急性和慢性炎症性疾病中也起着主要作用。在炎症过程中血管会改变其表型(血管重塑)。在发炎的皮肤中,血管重塑表现为血管网络通透性增加、扩张,血流量增加,以及炎症细胞的流入。在慢性炎症期间,活化的内皮细胞表达黏附分子、细胞因子和其他导致白细胞滚动、附着并迁移到皮肤中的分子。最近的研究表明,抑制血管活化具有强大的抗炎特性。因此,抗血管生成药物可能用于治疗炎症性疾病。特别是,局部应用抗血管生成药物可能非常适合规避血管生成抑制剂全身治疗的不良反应。我们最近的结果表明,刺激淋巴管生长和功能意外地成为治疗慢性炎症性疾病的一种新方法。