Angiogenic and lymphangiogenic factors in wound healing

When any tissue is damaged, multiple cells and tissues work towards the repair of the wounded site. Blood and lymphatic vessels are particularly important for the regeneration and healing of tissues. Angiogenesis is the process by which new blood vessels are formed. Angiogenesis is induced by angiogenic factors such as vascular endothelial growth factor (VEGF)-A which plays an important role in the repair of the damaged site. VEGF-A is expressed by macrophages, but pericytes also promote vascularization by expressing VEGF-A. In addition to VEGF-A, wound-related macrophages express tumor necrosis factor-α, Platelet-derived growth factor-bb, Interleukin (IL)-1, IL-6, and transforming growth factor β, and act on other cells. Pericytes change properties depending on the stage of the wound. For lymphangiogenesis, the expression of VEGF-C or -D, which are lymphatic endothelial growth factors, is the most important. Lymphatic vessel endothelial hyaluronan receptor-1-positive macrophages, which appear in the stroma, are also actively involved in lymphangiogenesis. On the other hand, podoplanin-positive myofibroblasts are indirectly involved in wound healing by being affecting in leukocyte migration as an “extravascular pathway”.