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Published on: May 14, 2013
Endostatin inhibits ischemia-induced neovascularization and increases ischemic tissue loss
Michael Dobryansky1, Robert D Galiano, Curtis L Cetrulo
1Laboratory for Microvascular Research and Vascular Tissue Engineering, New York University School of Medicine, New York, NY, USA.
Abstract:
The impact of inhibitors of tumor angiogenesis (endostatin, angiostatin) on the neovascularization required for the healing of transferred tissue has not been examined. We investigated the effect of endostatin on the functional neovascularization of random pattern flaps. C57BL6 mice were pretreated with endostatin beginning 3 days prior to surgery (n = 10), and daily injections continued throughout the study. Dorsal random cutaneous flaps were raised in both treatment and control (saline-treated) groups. The remaining cranial attachment was divided on day 9. Oxygen tension (PO2) was measured using a microprobe on days 1, 3, 5 and 16. Flaps were harvested and the vasculature was stained with CD31 on day 16. We found that endostatin significantly decreased flap survival. Mice that were treated with endostatin had fewer CD31+ blood vessels, worse flap perfusion at all time points, and lower oxygen tensions throughout the length of the flap. These findings have potential implications for the patients undergoing antiangiogenesis therapy who require surgical reconstruction.
Insights
Tumor angiogenesis inhibitors like endostatin impair wound healing by reducing blood vessel formation. This study shows endostatin significantly decreased flap survival and perfusion in mice.
Area of Science:
- Vascular Biology
- Tissue Engineering
- Oncology
Background:
- Tumor angiogenesis inhibitors are crucial in cancer therapy.
- Their impact on wound healing and tissue survival is not well understood.
- Neovascularization is vital for the success of transferred tissues.
Purpose of the Study:
- To investigate the effect of endostatin on functional neovascularization in random pattern skin flaps.
- To assess the impact of endostatin on flap survival and perfusion.
Main Methods:
- C57BL6 mice were pretreated with endostatin or saline.
- Random pattern dorsal cutaneous flaps were raised.
- Flap survival, oxygen tension (PO2), and vascularization (CD31 staining) were assessed.
Main Results:
- Endostatin significantly decreased flap survival.
- Fewer CD31+ blood vessels were observed in endostatin-treated flaps.
- Flap perfusion and oxygen tension were significantly lower in the endostatin group.
Conclusions:
- Endostatin impairs functional neovascularization and flap survival.
- These findings suggest caution when using antiangiogenesis therapy in patients requiring surgical reconstruction.
- Further research is needed to understand the clinical implications for reconstructive surgery.
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