Table 1.

Hedgehog in the ischemic skeletal muscle.

Result	First Author	Journal and Year of Publication	Ref.
Hindlimb ischemia induces Shh and Ptch upregulation in mice	Pola	Circulation, 2003	[13]
Hh inhibition with 5E1 antibody decreases upregulation of VEGF in response to ischemia	Pola	Circulation, 2003	[13]
Gli3-haploinsufficient (Gli3+/−) mice have reduced capillary density after induction of hindlimb ischemia	Renault	Circulation Res, 2009	[17]
None of the Hh ligands is able to induce Gli-target genes in endothelial cells Shh, Dhh, and Ihh proteins promote endothelial cell tubulogenesis and cytoskeletal rearrangement through non-canonical Hh pathways	Chinchilla	Cell Cycle, 2010	[24]
Endothelial-specific Smo knockout (eSmonull) mice do not have reduced angiogenic response to ischemia	Gupta	Lab Invest, 2018	[26]
Inhibition of the endogenous Shh pathway in Shh inducible knock out (Shh iKO) mice does not impair angiogenic response to ischemia Inflammation and macrophage recruitment are increased in the ischemic skeletal muscle when the endogenous Shh pathway is inhibited in Shh iKO mice	Caradu	Cardiovasc Res, 2018	[30]
Intraperitoneal injection of Shh recombinant protein enhances angiogenic response to ischemia in aged mice	Pola	Nature Med, 2001	[9]
Intramuscular treatment with a plasmid encoding the Shh human gene (phShh) enhances angiogenic response to ischemia in aged mice	Straface	J Cell Mol Med, 2009	[27]
Intramuscular treatment with phShh enhances skeletal muscle regeneration in aged mice	Piccioni	J Gerontol A Biol Sci Med Sci, 2014	[28]
Intramuscular treatment with phShh increases the number of bone marrow (BM)-derived endothelial progenitor cells (EPCs) in response to ischemia in mice	Palladino	Molecular Therapy, 2011	[15]
Combined therapy with phShh and BM-derived EPCs enhances angiogenesis and myogenesis in the murine ischemic skeletal muscle	Palladino	J Vasc Res, 2012	[36]
Treatment with an Shh receptor agonist (SAG) restores number and function of EPCs in diabetic mice and increases neovascularization in response to ischemia	Qin	Mol Cell Endocrinol, 2016	[37]
Dhh gene therapy enhances angiogenesis in the ischemic muscle of aged mice through promotion of peripheral nerve survival	Renault	Circulation Res, 2013	[16]
Treatment with a Dhh-signaling agonist (SAG) improves endothelial function in diabetic mice without promoting angiogenesis	Caradu	Circulation Res, 2018	[31]
Microparticles carrying Shh are increased in humans with peripheral artery disease	Giarretta	Int J Mol Sci, 2018	[29]