Desert hedgehog promotes ischemia-induced angiogenesis by ensuring peripheral nerve survival.
Circ Res
; 112(5): 762-70, 2013 Mar 01.
Article
in En
| MEDLINE
| ID: mdl-23343527
ABSTRACT
RATIONALE Blood vessel growth and patterning have been shown to be regulated by nerve-derived signals. Desert hedgehog (Dhh), one of the Hedgehog family members, is expressed by Schwann cells of peripheral nerves. OBJECTIVE:
The purpose of this study was to investigate the contribution of Dhh to angiogenesis in the setting of ischemia. METHODS ANDRESULTS:
We induced hindlimb ischemia in wild-type and Dhh(-/-) mice. First, we found that limb perfusion is significantly impaired in the absence of Dhh. This effect is associated with a significant decrease in capillary and artery density in Dhh(-/-). By using mice in which the Hedgehog signaling pathway effector Smoothened was specifically invalidated in endothelial cells, we demonstrated that Dhh does not promote angiogenesis by a direct activation of endothelial cells. On the contrary, we found that Dhh promotes peripheral nerve survival in the ischemic muscle and, by doing so, maintains the pool of nerve-derived proangiogenic factors. Consistently, we found that denervation of the leg, immediately after the onset of ischemia, severely impairs ischemia-induced angiogenesis and decreases expression of vascular endothelial growth factor A, angiopoietin 1, and neurotrophin 3 in the ischemic muscle.CONCLUSIONS:
This study demonstrates the crucial roles of nerves and factors regulating nerve physiology in the setting of ischemia-induced angiogenesis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peripheral Nerves
/
Neovascularization, Physiologic
/
Hedgehog Proteins
/
Hindlimb
/
Ischemia
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Circ Res
Year:
2013
Document type:
Article
Affiliation country:
France