Lack of alpha2-antiplasmin improves cutaneous wound healing via over-released vascular endothelial growth factor-induced angiogenesis in wound lesions.

Abstract

BACKGROUND:

The fibrinolytic system is supposed to play an important role in the degradation of extracellular matrices for physiological and pathological tissue remodeling; however, the detailed mechanism regarding how this system affects cutaneous wound healing remains to be clarified.

METHODS AND RESULTS:

We performed experimental cutaneous wounding in mice with a deficiency of alpha(2)-antiplasmin (alpha(2)AP), which is a potent and specific plasmin inhibitor. We found that an accelerated wound closure was observed in alpha(2)AP-deficient (alpha(2)AP-/-) mice in comparison with wild type (WT) mice. Moreover, we observed that a greater increase of angiogenesis occurred in the process of wound healing in alpha(2)AP-/- mice than in the WT mice. Intriguingly, mRNA expression of vascular endothelial growth factor (VEGF), which is the best characterized positive regulator of angiogenesis, in wound lesions was found to show a greater increase in the early phase of the healing process in alpha(2)AP-/- mice than in WT mice. In addition, the amount of released-VEGF from the explanted fibroblasts of alpha(2)AP-/- mice increased dramatically more than in the WT mice. Finally, the intra-jugular administration of anti-VEGF antibody clearly suppressed the increased angiogenesis and accelerated wound closure in the wound lesion of alpha(2)AP-/- mice.

CONCLUSION:

The lack of alpha(2)AP markedly causes an over-release of VEGF from the fibroblasts in cutaneous wound lesions, thereby inducing angiogenesis around the area, and thus resulting in an accelerated-wound closure.

CONCLUSIONS:

This is the first report to describe the crucial role that alpha(2)AP plays following angiogenesis in the process of wound healing. Our results provide new insight into the role of alpha(2)AP on cutaneous wound healing.

• Authors: Y Kanno, K Hirade, A Ishisaki, K Nakajima, H Suga, T Into, K Matsushita, K Okada, O Matsuo, H Matsuno
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 4 Issue 7 Pg. 1602-10 (Jul 2006) ISSN: 1538-7933 [Print] England
• PMID: 16839360 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Vascular Endothelial Growth Factor A
• alpha-2-Antiplasmin

Topics

• Animals
• Mice
• Mice, Knockout
• Neovascularization, Physiologic (physiology)
• Skin (injuries)
• Time Factors
• Vascular Endothelial Growth Factor A (genetics, physiology)
• Wound Healing (physiology)
• Wounds and Injuries (pathology)
• alpha-2-Antiplasmin (deficiency)