Dimethyloxalylglycine stabilizes HIF-1α in cultured human endothelial cells and increases random-pattern skin flap survival in vivo.

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.

• Authors: Maziar Shafighi, Radu Olariu, Ali R Fathi, Siamak Djafarzadeh, Stephan M Jakob, Andrej Banic, Mihai A Constantinescu
• Journal: Plastic and reconstructive surgery (Plast Reconstr Surg) Vol. 128 Issue 2 Pg. 415-422 (Aug 2011) ISSN: 1529-4242 [Electronic] United States
• PMID: 21788833 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Amino Acids, Dicarboxylic
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• oxalylglycine

Topics

• Amino Acids, Dicarboxylic (pharmacology)
• Animals
• Cells, Cultured
• Disease Models, Animal
• Endothelial Cells (cytology, drug effects, metabolism)
• Endothelium, Vascular (cytology, drug effects, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Follow-Up Studies
• Graft Survival (drug effects)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (drug effects, metabolism)
• Laser-Doppler Flowmetry
• Male
• Rats
• Rats, Wistar
• Skin Transplantation
• Surgical Flaps (blood supply)
• Umbilical Veins (cytology)