Angiogenesis and lymphangiogenesis in inflammatory skin disorders.
Angiogenesis, the growth of new blood vessels from pre-existing vessels, occurs physiologically in wound healing, during inflammatory diseases, and in tumor growth. Lymphangiogenesis can be activated in inflammation and tumor metastasis. The family of vascular endothelial growth factors (VEGFs) and angiopoietins are essential for angiogenesis and lymphangiogenesis. The angiogenic process is tightly regulated by VEGFs, angiopoietins, and endogenous inhibitors. VEGFs and angiopoietins exert their effects by activating specific receptors present on blood and lymphatic endothelial cells. There is now compelling evidence that cells of innate and adaptive immunity (macrophages, mast cells, neutrophils, eosinophils, lymphocytes) are a major source of angiogenic and lymphangiogenic factors. Chronic inflammatory skin diseases such as psoriasis and atopic dermatitis are characterized by altered angiogenesis, lymphangiogenesis, or both. Also such acute inflammatory skin disorders as urticaria, ultraviolet B-induced damage, and angioedema are associated with changes in angiogenic factors. In systemic sclerosis there is a switch from proangiogenic to antiangiogenic factors that play a role in the defective vascular process of this disorder. As yet, there are no clinical trials showing that canonical VEGF/VEGF receptor-targeted strategies can modulate inflammatory skin diseases. Novel strategies targeting other angiogenic/lymphangiogenic pathways should also be investigated.
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples, Naples, Italy.
Gilda
G
Varricchi
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples, Naples, Italy.
Francescopaolo
F
Granata
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples, Naples, Italy.
Stefania
S
Loffredo
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples, Naples, Italy.
Arturo
A
Genovese
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples, Naples, Italy. Electronic address: marone@unina.it.
Gianni
G
Marone
D000208:Acute Disease; D002908:Chronic Disease; D003872:Dermatitis / Q000473:pathology*; D006801:Humans; D042583:Lymphangiogenesis; D009389:Neovascularization, Pathologic; D012867:Skin / Q000098:blood supply* / Q000473:pathology*
angioedema; angiogenesis; atopic dermatitis; interleukin-17; lymphangiogenesis; macrophages; mast cells; psoriasis; urticaria; vascular endothelial growth factor