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Endothelial Cell Tube Formation Assay for the In Vitro Study of Angiogenesis
Published on: September 1, 2014
The angiogenesis inhibitor endostatin impairs blood vessel maturation during wound healing
Abstract:
Endostatin is a cleavage product of collagen XVIII that strongly inhibits tumor angiogenesis. To determine if endostatin affects other angiogenic processes, we generated full-thickness excisional wounds on the back of mice that were systemically treated with recombinant murine endostatin. No macroscopic abnormalities of the wound healing process were observed. Histological analysis revealed normal wound contraction and re-epithelialization, but a slight reduction in granulation tissue formation and reduced matrix deposition at the wound edge. The blood vessel density in the wounds of endostatin-treated mice was not affected. However, ultrastructural analysis demonstrated severe abnormalities in blood vessel maturation. The wound vessels in the endostatin-treated mice were narrowed or closed with an irregular luminal surface, resulting in a severe reduction in the number of functional vessels and extravasation of erythrocytes. Endostatin treatment did not affect the expression level and localization of collagen XVIII mRNA and protein. Furthermore, the angiogenesis regulators vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 were normally expressed in the wounds of endostatin-treated mice. However, expression of the major wound matrix proteins fibronectin and collagens I and III was significantly reduced. This reduction is likely to explain the reduced density of the wound matrix. Our results demonstrate that endostatin treatment reduces the number of functional blood vessels and the matrix density in the granulation tissue, but does not significantly affect the overall wound healing process.
Insights
Endostatin treatment in mice reduced functional blood vessels and matrix density in wounds. However, overall wound healing, including contraction and re-epithelialization, remained largely unaffected.
Area of Science:
- Biomedical research
- Wound healing studies
- Angiogenesis research
Background:
- Endostatin, a collagen XVIII cleavage product, is known to inhibit tumor angiogenesis.
- The effect of endostatin on physiological angiogenic processes, such as wound healing, requires further investigation.
Purpose of the Study:
- To investigate the impact of systemic endostatin administration on the wound healing process in mice.
- To assess endostatin's effects on angiogenesis, vascular maturation, and extracellular matrix deposition during wound repair.
Main Methods:
- Full-thickness excisional wounds were created in mice systemically treated with recombinant murine endostatin.
- Wound healing was evaluated through macroscopic, histological, and ultrastructural analyses.
- Expression levels of collagen XVIII, vascular endothelial growth factor, angiopoietins, fibronectin, and collagens I/III were assessed.
Main Results:
- Macroscopic wound healing, contraction, and re-epithelialization were not significantly altered.
- Histology showed reduced granulation tissue formation and matrix deposition.
- Ultrastructural analysis revealed severe abnormalities in blood vessel maturation, leading to fewer functional vessels, despite normal overall blood vessel density.
- Expression of key angiogenesis regulators remained normal, but major wound matrix proteins were reduced.
Conclusions:
- Systemic endostatin treatment impairs blood vessel maturation and reduces matrix density in wound granulation tissue.
- Despite these vascular and matrix alterations, endostatin does not significantly impede the overall wound healing process in mice.
- These findings suggest a complex role for endostatin in physiological angiogenesis and tissue repair.
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