Skip Navigation LinksHome > August 2011 - Volume 128 - Issue 2 > Dimethyloxalylglycine Stabilizes HIF-1α in Cultured Human En...
Plastic & Reconstructive Surgery:
doi: 10.1097/PRS.0b013e31821e6e69
Experimental: Original Articles

Dimethyloxalylglycine Stabilizes HIF-1α in Cultured Human Endothelial Cells and Increases Random-Pattern Skin Flap Survival In Vivo

Shafighi, Maziar M.D.; Olariu, Radu M.D.; Fathi, Ali R. M.D.; Djafarzadeh, Siamak Ph.D.; Jakob, Stephan M. M.D., Ph.D.; Banic, Andrej M.D., Ph.D.; Constantinescu, Mihai A. M.D.

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Abstract

Background: The goal of this study was to evaluate in vitro and in vivo the effects of up-regulation of the proangiogenic hypoxia inducible factor (HIF)-1α induced by dimethyloxalylglycine on endothelial cell cultures and on skin flap survival.

Methods: Human umbilical vein endothelial cell cultures were exposed to hypoxic conditions, to dimethyloxalylglycine, and to cobalt chloride for up to 24 hours. Expression of HIF-1α and vascular endothelial growth factor (VEGF) in cell culture media was analyzed. In vivo, 20 male Wistar rats were assigned randomly to either the treatment group (dimethyloxalylglycine intraperitoneal injection, n = 10) or the control group (saline intraperitoneal injection, n = 10). A dorsal skin flap was raised in all animals and sutured back into place. Flap survival was evaluated on postoperative day 7 by laser Doppler and digital planimetry.

Results: In vitro treatment of human umbilical vein endothelial cells during a 24-hour period showed a significant elevation of VEGF expression with dimethyloxalylglycine exposure (92 ± 35 pg/mg total cellular protein) or hypoxia exposure (88 ± 21 pg/mg total cellular protein) compared with controls (23 ± 10 pg/mg total cellular protein) (p < 0.05 for both). In vivo experiments showed a significant decrease of flap necrosis in the treatment group animals versus controls (35.95 ± 5.03 percent versus 44.42 ± 5.18 percent, p < 0.05). The laser Doppler evaluation revealed significantly increased blood flow in the proximal two-thirds of the flap in the treatment group compared with the control group (p < 0.05).

Conclusion: Dimethyloxalylglycine treatment significantly increases VEGF and HIF-1α expression in endothelial cell cultures and enhances skin flap survival in vivo in a rat model.

©2011American Society of Plastic Surgeons

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