Table 2.

Hedgehog in the ischemic heart.

Result	First Author	Journal and Year of Publication	Ref.
Ischemia induces upregulation of Shh protein in the adult mouse heart	Kusano Bijlsma Xiao	Nature Med, 2005 Exp Biol Med, 2008 Cardiovasc Res, 2012	[38] [39] [40]
HIF-1α is responsible for Hh activation in hypoxic cardiomyoblasts	Hwang Bijlsma	Mol Cell Biochem, 2008 J C Mol Med, 2009	[41] [18]
Endogenous Hh expression does not induce vascularization, but rather increases apoptosis and reduces fibrosis in murine ischemic myocardium	Bijlsma	Exp Biol Med, 2008	[39]
Hh signaling is required for the maintenance of the adult coronary vasculature Endogenous Hh signaling reduces infarct area and increases border zone coronary vessel density after myocardial infarction in mice	Lavine	J Clin Invest, 2008	[42]
Gli3-haploinsufficient (Gli3+/-) mice have reduced capillary density and left ventricular ejection fraction after myocardial infarction	Renault	Circulation Res, 2009	[17]
Upregulation of Shh, Ptch, and Gli1 is impaired in the ischemic myocardium of diabetic mice	Xiao	Cardiovasc Res, 2012	[40]
Canonical Shh signaling regulates gene transcription in cardiomyocytes	Carbe	Am J Physiol Heart Circ Physiol, 2014	[44]
Treatment with an Shh pathway agonist (SAG) enhances capillary density, reduces infarct size, and improves cardiac function in diabetic mice with myocardial infarction	Xiao	Cardiovasc Res, 2012	[40]
Intramyocardial gene transfer of phShh induces production of angiogenic growth factors, enhances neovascularization, reduces fibrosis, and preserves left ventricular function in rabbit and pig models of acute and chronic myocardial ischemia	Kusano	Nature Med, 2005	[38]
Injection in the rat ischemic myocardium of Shh-overexpressing mesenchymal stem cells (MSCs) increases blood vessel density and preserves function of the left ventricle	Ahmed	PLoS One, 2010	[45]
Intramyocardial gene transfer of phShh increases the number of bone marrow BM-EPCs and their differentiation into endothelial cells in the myocardium	Kusano	Nature Med, 2005	[38]
In a rat model of ischemia-reperfusion, stimulation of Shh pathway (by a recombinant peptide or microparticles harboring Shh) reduces infarct size and arrhythmias	Paulis	Sci Rep, 2015	[47]