Safrole-2', 3'-oxide induces atherosclerotic plaque vulnerability via ATF4/p75NTR/IL8 path

• 作 者: DiGe[1]LeSu[1]JingZhao[1]HaiyanZhang[1]ShangliZhang[1]YunZhang[2]BaoxiangZhao[3]JunyingMiao[1]
• 机 构: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology,School of Life Science,
• 出 处: International Conference for Physiological Sciences 2012(201
• 发表日期: 2012年期

　　Safrole-2,3-oxide (SFO) is the electrophilic metabolite of safrole, a natural plant constituent found in oils of numerous edible herbs and spices.The effects of SFO in cardiovascular system are little known.In this study, SFO treatment changed the lesion composition to an unstable phenotype and damaged the endothelium in plaques.By using gene microarray, we identified the levels of p75 neurotrophin receptor (p75NTR), activating transcription factor 4 (ATF4) and interleukin 8 (IL-8) greatly increased with SFO treatment in human endothelial cells.Furthermore, SFO increased the plaque endothelium level of p75NTR, the serum level of KC (a functional homolog of IL-8 in mice) and the number of apoptotic cells in plaque in apoE-/-mice.siRNA knockdown of p75NTR inhibited the IL-8 increase and siRNA knockdown of ATF4 inhibited the SFO-induced increase in p75NTR expression.Thus, SFO contributes to the instability of atherosclerotic plaque in apoE-/-mice by activating an ATF4/p75NTR/IL-8 signal pathway and cell apoptosis in plaque.