Vascular endothelial growth factor receptor-3 in lymphangiogenesis in wound healing

Vascular endothelial growth factor receptor-3 (VEGFR-3) is essential for em bryonic cardiovascular development, but thereafter becomes confined to the lymphatic endothelium in adult tissues. We have here studied VEGFR-3 expres sion in experimental wounds of pigs and chronic inflammatory wounds of huma ns. In healing incisional and punch biopsy wounds made in the dorsal skin o f pigs, angiogenic blood vessels, identified by use of the blood vascular e ndothelial markers vWF: and PAL-E and the basal lamina protein laminin, dev eloped into the granulation tissue stroma from day 4 onward, being most abu ndant on days 5 and 6 and regressing thereafter. VEGFR-3-positive vessels w ere observed in the granulation tissue from day 5 onward. These vessels wer e distinct from the PAL-E/laminin/vWF-positive vessels and fewer in number, and they appeared to sprout from pre-existing VEGFR-3-positive lymphatic v essels at the wound edge. Unlike the blood vessels, very few VEGFR-3-positi ve lymphatic vessels persisted on day 9 and none on day 14. In chronic woun ds such as ulcers and decubitus wounds of the lower extremity of humans, VE GFR-3 was also weakly expressed in the vascular endothelium. Our results su ggest that transient lymphangiogenesis occurs in parallel With angiogenesis in healing wounds and that VEGFR-3 becomes up-regulated in blood vessel en dothelium in chronic inflammatory wounds.