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- Title
The morphogen Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors.
- Authors
Pola, R; Ling, L E; Silver, M; Corbley, M J; Kearney, M; Blake Pepinsky, R; Shapiro, R; Taylor, F R; Baker, D P; Asahara, T; Isner, J M
- Abstract
Sonic hedgehog (Shh) is a prototypical morphogen known to regulate epithelial/mesenchymal interactions during embryonic development. We found that the hedgehog-signaling pathway is present in adult cardiovascular tissues and can be activated in vivo. Shh was able to induce robust angiogenesis, characterized by distinct large-diameter vessels. Shh also augmented blood-flow recovery and limb salvage following operatively induced hind-limb ischemia in aged mice. In vitro, Shh had no effect on endothelial-cell migration or proliferation; instead, it induced expression of two families of angiogenic cytokines, including all three vascular endothelial growth factor-1 isoforms and angiopoietins-1 and -2 from interstitial mesenchymal cells. These findings reveal a novel role for Shh as an indirect angiogenic factor regulating expression of multiple angiogenic cytokines and indicate that Shh might have potential therapeutic use for ischemic disorders.
- Publication
Nature medicine, 2001, Vol 7, Issue 6, p706
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/89083