The Cutaneous Vascular System in Chronic Skin Inflammation

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.