TRAIL inhibits oxidative stress in human aortic endothelial cells exposed to pro-inflammatory stimuli.
TRAIL inhibits oxidative stress in human aortic endothelial cells exposed to pro-inflammatory stimuli.
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DOI：
10.14814/phy2.14612
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发表时间：
2020-10
影响因子：
2.5
通讯作者：
Cummins PM
中科院分区：
文献类型：
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作者：
Forde H;Harper E;Rochfort KD;Wallace RG;Davenport C;Smith D;Cummins PM
研究表明，肿瘤坏死因子相关凋亡诱导配体（TRAIL）具有血管保护潜力，因为低水平的TRAIL会加速血管钙化，而外源性TRAIL给药则具有抗动脉粥样硬化活性。TRAIL介导的血管保护机制尚不清楚。我们研究了TRAIL（100 ng/ml）对暴露于致动脉粥样硬化条件下的人主动脉内皮细胞（HAEC）的影响;（a）使用ibidi µ-载玻片流体系统的振荡剪切应力（±10达因/cm 2）;（B）促炎性损伤，即肿瘤坏死因子α（TNF-α，100 ng/ml）和高血糖症（30 mM d-葡萄糖）。检查的终点包括炎症基因表达和活性氧（ROS）形成。TRAIL将HAECs暴露于振荡剪切应力时的净基因表达向抗氧化表型转移。TRAIL显著减少暴露于TNF-α和高血糖的HAEC中的ROS形成。因此，TRAIL似乎至少部分地通过减少氧化应激而对内皮赋予动脉粥样硬化保护作用。在存在和不存在促炎性刺激（肿瘤坏死因子α和高脂血症）的情况下，用重组TRAIL处理人主动脉内皮细胞（HAEC）。TRAIL减少了暴露于促炎、促动脉粥样硬化条件的HAEC中的活性氧簇形成。
Studies suggest that tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) has vasoprotective potential, as low levels of TRAIL cause accelerated vascular calcification, whereas exogenous TRAIL administration exhibits anti‐atherosclerotic activity. The mechanism of TRAIL‐mediated vasoprotection remains unclear. We studied the effects of TRAIL (100 ng/ml) on human aortic endothelial cells (HAECs) exposed to pro‐atherogenic conditions; (a) oscillatory shear stress (±10 dynes/cm2) using the ibidi µ‐slide fluidic system; (b) pro‐inflammatory injury, that is, tumor necrosis factor alpha (TNF‐α, 100 ng/ml) and hyperglycemia (30 mM d‐glucose). End‐points examined included inflammatory gene expression and reactive oxygen species (ROS) formation. TRAIL shifted the net gene expression toward an antioxidant phenotype in HAECs exposed to oscillatory shear stress. TRAIL significantly reduced ROS formation in HAECs exposed to both TNF‐α and hyperglycemia. Therefore, TRAIL appears to confer atheroprotective effects on the endothelium, at least in part, by reducing oxidative stress. Human aortic endothelial cells (HAECs) were treated with recombinant TRAIL in the presence and absence of pro‐inflammatory stimuli (Tumour necrosis factor alpha and hyperglycaemia). TRAIL reduced reactive oxygen species formation in HAECs exposed to pro‐inflammatory, pro‐atherogenic conditions.