The hedgehog signaling pathway, a new therapeutic target for treatment of ischemic heart disease.

ABSTRACT

The hedgehog (Hh) protein is involved in angiogenesis and cardiovascular development via activation of the classical ligand-dependent signaling transduction. So its potential therapeutic meaning of Hh signaling proteins to the ischemic heart diseases has been greatly explored. Recent studies show that up-regulated expression of hypoxia-induced factor-1 (HIF-1) and inflamemation in ischemic tissues activate the Hh signaling cascade in a GLI-dependent or independent way, resulting in elevated expression levels of pro-angiogenic and agiogenic factors to facilitate angiogenesis. In addition, Hh signaling pathway activation can promote residual myocardial progenitors, endogenous EPCs and MSCs differentiating into cardiomyocytes, inhibit cardiomyocyte apoptosis; thirdly, high level of exogenous Hh signaling can reduce myocardial ischemic/reperfusion injuries(I/R). In conclusion, three kinds of mechanisms induced by Hh signaling pathway participate in the heart repair after myocardial ischemia. Therefore, Hh agonists including Hh protein, Hh gene transfer and small molecule agonist could be part of a potential therapeutic strategy for acute or chronic ischemic heart disease.