| First Author | Renault MA | Year | 2013 |
| Journal | Circ Res | Volume | 112 |
| Issue | 5 | Pages | 762-70 |
| PubMed ID | 23343527 | Mgi Jnum | J:213333 |
| Mgi Id | MGI:5584097 | Doi | 10.1161/CIRCRESAHA.113.300871 |
| Citation | Renault MA, et al. (2013) Desert hedgehog promotes ischemia-induced angiogenesis by ensuring peripheral nerve survival. Circ Res 112(5):762-70 |
| abstractText | 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 AND RESULTS: 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. |
