Protective effect of sonic hedgehog against oxidized low‑density lipoprotein‑induced endothelial apoptosis: Involvement of NF‑κB and Bcl‑2 signaling

Sonic hedgehog (Shh) is pivotally important in embryonic and adult blood vessel development and homeostasis. However, whether Shh is involved in atherosclerosis and plays a role in endothelial apoptosis induced by oxidized lowdensity lipoprotein (oxLDL) has not been reported. The present study used recombinant ShhN protein (rShhN) and a plasmid encoding the human Shh gene (phShh) to investigate the role of Shh in oxLDLmediated human umbilical vein endothelial cell (HUVEC) apoptosis. The present study found that oxLDL was able to induce apoptosis in HUVECs and that Shh protein expression was downregulated. Furthermore, pretreatment with rShhN or transfection with phShh increased antiapoptosis protein Bcl2 expression and decreased cell apoptosis. These protective effects of rShhN could be abolished by cyclopamine, which is a hedgehog signaling inhibitor. Furthermore, a coimmunoprecipitation assay was performed to demonstrate that Shh interacted with NFkappaB p65 in HUVECs. Additionally, oxLDL upregulated the phosphorylation of NFkappaB p65 and inhibitor of NFkappaBalpha (IkappaBalpha), and these effects decreased notably following rShhN and phShh treatment. Together, the present findings suggested that Shh serves an important protective role in alleviating oxLDLmediated endothelial apoptosis by inhibiting the NFkappaB signaling pathway phosphorylation and Bcl2 mediated mitochondrial signaling.