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(American Journal of Pathology. 2006;169:1080-1087.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.051251

Vascular Endothelial Growth Factor-C Accelerates Diabetic Wound Healing

Anne Saaristo*{dagger}, Tuomas Tammela*, Anniina Farkkila*, Marika Kärkkäinen*, Erkki Suominen{dagger}, Seppo Yla-Herttuala{ddagger} and Kari Alitalo*

From the Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research,* Biomedicum Helsinki and Helsinki University Central Hospital, University of Helsinki, Helsinki; the Department of Plastic Surgery,{dagger} Turku University Central Hospital, Turku; and the Department of Medicine and Gene Therapy Unit,{ddagger} A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland

Diabetes impairs numerous aspects of tissue repair. Failure of wound angiogenesis is known to delay diabetic wound healing, whereas the importance of lymphangiogenesis for wound healing is unclear. We have examined whether overexpression of vascular endothelial growth factor (VEGF)-C via an adenoviral vector could improve the healing of full-thickness punch biopsy wounds in genetically diabetic (db/db) mice. We found that VEGF-C enhanced angiogenesis and lymphangiogenesis in the wound and significantly accelerated wound healing in comparison to the control wounds. VEGF-C also recruited inflammatory cells, some of which expressed VEGFR-3. On the other hand, when the function of endogenous VEGF-C/VEGF-D was blocked with a specific inhibitor, wound closure was delayed even further. These results suggest a function for VEGF-C in wound healing and demonstrate the therapeutic potential of VEGF-C in the treatment of diabetic wounds.




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Copyright © 2006 by the American Society for Investigative Pathology.