The Role of Smoothened and Hh Signaling in Neovascularization

  • Raffaella Soleti
  • Ramaroson Andriantsitohaina
  • Maria Carmen MartínezEmail author
Part of the Topics in Medicinal Chemistry book series (TMC, volume 16)


New vessel formation plays a key role not only in physiological processes such as embryonic development and wound repair but also during several pathological situations. In this respect, favoring neovascularization represents a promising therapeutic approach that would allow inducing tissue repair. Among the candidate proteins able to modulate neovascularization, evidence show that the administration of recombinant hedgehog (Hh) protein, gene, or cell therapy based on Hh transfer or using extracellular vesicles as vectors enhance new vessel formation. Here, we summarized the role of Hh pathway on angiogenesis and its therapeutic potential during myocardial infarction and diabetes.


Extracellular vesicles Hedgehog Neovascularization Smoothened 



AMP-activated protein kinase

Ang(1, 2)

Angiopoietin(1, 2)


Circulating endothelial cells


Desert hedgehog


Extracellular matrix


Endothelial nitric oxide synthase


Extracellular signal-regulated kinase


Focal adhesion kinase


Fibroblast growth factor

Gli(1, 2, 3)

Glioma-associated oncogenes(1, 2, 3)


G-protein-coupled receptors




Hypoxia-inducible factor-1


Indian hedgehog


Inducible nitric oxide synthase


c-Jun N-terminal kinase


Leucine-rich repeat G-protein-coupled receptor 5


Lymphocytic microparticles


Mitogen-activated protein kinase






Microparticles expressing sonic hedgehog


Messenger RNA


Nitric oxide


Platelet-derived growth factor


Platelet-endothelial cell-adhesion molecule-1


Plasmid encoding the sonic hedgehog human gene


Phosphatidylinositol 3-kinase


Protein kinase C




Rho-associated protein kinase


Reactive oxygen species


Stromal cell-derived factor-1


Sonic hedgehog




Transforming growth factor β




Thymidine phosphorylase


Vascular endothelial cadherin


Vascular endothelial growth factor

VEGFR(−1, −2)

Vascular endothelial growth factor receptor(−1, −2)


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Raffaella Soleti
    • 1
  • Ramaroson Andriantsitohaina
    • 1
    • 2
  • Maria Carmen Martínez
    • 1
    • 3
    Email author
  1. 1.INSERM UMR1063, Stress oxydant et pathologies métaboliquesAngersFrance
  2. 2.Centre Hospitalier Universitaire d’AngersAngersFrance
  3. 3.Institut de Biologie en SantéAngersFrance

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