Abstract 10259: Schwann Cell-Derived Desert Hedgehog Controls Limb Blood Vessel Network and Angiogenesis
The Hedgehog (Hh) family of morphogens was shown to regulate blood vessel maintenance and growth in adults, but the identity of the Hh protein involved in this process has not been characterized. Because angiogenesis is known to be regulated by peripheral nerve-derived signals, we hypothesized that Schwann cell-derived Desert Hedgehog (Dhh) may regulate blood vessel homeostasis in adults. The purpose of this study is to investigate the role of Dhh in blood vessel maintenance and growth in adults.
Methods and results: We found that Dhh which is expressed by peripheral nerves is the main Hh expressed in the skeletal muscle of adult mice. By using immunohistology and microCT analyses we showed that, in the skeletal muscle of Dhh-/- mice, the number of vessels is decreased and their organization is impaired demonstrating that Dhh is necessary to established and/or maintain the limb vasculature network in physiologic conditions. To investigate the role of Dhh in adult vessel growth, we compared hind limb ischemia-induced angiogenesis in Dhh-/- mice and in their WT littermates. First, we found that limb perfusion and muscle repair are significantly impaired in the absence of Dhh. This effect was associated with a significant decrease in capillary (12±1 vs 27±2 CD31 positive capillaries/HPF) and artery density (0.026±0.005 vs 0.111±0.010 Ø≥7µm arteries/µm3) in Dhh -/- versus WT respectively. Moreover, by using the mouse corneal angiogenesis model, we demonstrated for the first time that Dhh is proangiogenic. Thus those results demonstrate the major role of Dhh, at least through its proangiogenic effect, in vessel growth and tissue repair.
Conclusion: This study is the first demonstration of the essential role of nerve- derived Dhh in blood vessel maintenance and growth in adult skeletal muscle proposing Dhh as a new actor of the nerve - vessel crosstalk
- © 2011 by American Heart Association, Inc.