Open AccessProtective effect of sonic hedgehog against oxidized low‑density lipoprotein‑induced endothelial apoptosis: Involvement of NF‑κB and Bcl‑2 signaling
Author(s) -
Heguang Huang,
Hanjie Yu,
Liang Lin,
Junming Chen,
Pengli Zhu
Publication year - 2020
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2020.4542
Subject(s) - cyclopamine , sonic hedgehog , apoptosis , microbiology and biotechnology , biology , hedgehog signaling pathway , signal transduction , downregulation and upregulation , transfection , umbilical vein , phosphorylation , chemistry , cancer research , biochemistry , gene , in vitro
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 low‑density lipoprotein (ox‑LDL) has not been reported. The present study used recombinant Shh‑N protein (rShh‑N) and a plasmid encoding the human Shh gene (phShh) to investigate the role of Shh in ox‑LDL‑mediated human umbilical vein endothelial cell (HUVEC) apoptosis. The present study found that ox‑LDL was able to induce apoptosis in HUVECs and that Shh protein expression was downregulated. Furthermore, pretreatment with rShh‑N or transfection with phShh increased anti‑apoptosis protein Bcl‑2 expression and decreased cell apoptosis. These protective effects of rShh‑N could be abolished by cyclopamine, which is a hedgehog signaling inhibitor. Furthermore, a co‑immunoprecipitation assay was performed to demonstrate that Shh interacted with NF‑κB p65 in HUVECs. Additionally, ox‑LDL upregulated the phosphorylation of NF‑κB p65 and inhibitor of NF‑κB‑α (IκBα), and these effects decreased notably following rShh‑N and phShh treatment. Together, the present findings suggested that Shh serves an important protective role in alleviating ox‑LDL‑mediated endothelial apoptosis by inhibiting the NF‑κB signaling pathway phosphorylation and Bcl‑2 mediated mitochondrial signaling.