Figure 2.

Hh in the ischemic heart. The mechanisms leading to the activation of the Hh pathway in the ischemic heart are not fully elucidated. It is likely that they depend on HIF-1α, but this has been demonstrated only in vitro. There is also evidence of a reciprocal activation of HIF-1α by Shh. Hh-dependent angiogenesis in the ischemic heart occurs indirectly, as it is mediated by the production of angiogenic growth factors by myocardial fibroblasts in response to Hh stimulation. Hh-responding fibroblasts also produce SDF1α, which is responsible for the recruitment of BM-EPCs in the ischemic area. There are in vitro data showing that Shh has the ability to regulate the transcriptional response of cardiomyocytes, with increased expression of genes involved in cell survival. Dashed lines and italic text represent in vitro data.