TNF-alpha and shear stress-induced large artery adaptations.
TNF-alpha and shear stress-induced large artery adaptations.
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TNF-α 和剪切应力诱导大动脉适应。
DOI：
10.1016/j.jss.2006.12.563
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Berceli,ScottA
中科院分区：
文献类型：
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作者：
Ozaki,CKeith;Jiang,Zhihua;Berceli,ScottA
背景肿瘤坏死因子-α (TNF-α) 上调与低剪切力和高剪切力诱导的动脉重塑有关。为了解决这一明显的悖论并定义大动脉中 TNF-α 信号传导的生物学，我们测试了 TNF-α 的差异时间表达驱动剪切调节动脉重塑的假设。 材料和方法通过手术在同一只兔子中为颈总动脉创建低剪切和高剪切环境。在 d0、d1、d3、d7 和 d14 后收获颈总动脉（总共 60 条），分析包括形态学、TNF-α 和 IL-10 mRNA 定量。在单独的实验中，动物通过短期或长期给药接受聚乙二醇化可溶性 TNF-α 1 型受体 (PEG sTNF-RI) 或载体，以确定 TNF-α 阻断的效果。 结果该模型产生 14 倍剪切差异 (P < 0.001)，低剪切下内侧增厚 (P = 0.025)，并有高剪切下向外重塑的证据 (P = 0.007)。第 1 天低剪切立即将 TNF-α 表达上调约 50 倍（P < 0.001）。相反，高剪切诱导的 TNF-α 表达延迟且持续（第 7 天为 22 倍，P = 0.012；第 14 天为 23 倍，P = 0.007）。低剪切和高剪切均逐渐诱导 IL-10 表达（分别为 P = 0.002 和 P = 0.004）。 TNF-α 信号传导的短期（5 天）和长期（14 天）阻断均不会导致治疗引起的低剪切或高剪切动脉重塑发生变化。结论：剪切应力在大动脉重塑中差异性地、暂时性地调节 TNF-α 表达。然而，TNF-α 阻断并没有显着影响最终的剪切诱导形态，这表明大动脉可以响应独立于 TNF-α 信号传导的血流扰动而进行重塑。
BACKGROUNDTumor necrosis factor-α (TNF-α) up-regulation has been associated with both low and high shear-induced arterial remodeling. To address this apparent paradox and to define the biology of TNF-α signaling in large arteries, we tested the hypotheses that differential temporal expression of TNF-α drives shear-regulated arterial remodeling.MATERIALS AND METHODSBoth low- and high-shear environments in the same rabbit were surgically created for common carotid arteries. Common carotid arteries (n = 60 total) were harvested after d0, d1, d3, d7, and d14 and analyses included morphology, TNF-α, and IL-10 mRNA quantitation. In separate experiments, animals received pegylated soluble TNF-α Type 1 receptor (PEG sTNF-RI) or vehicle via either short- or long-term dosing to define the effect of TNF-α blockade.RESULTSThe model yielded a 14-fold shear differential (P < 0.001) with medial thickening under low shear (P = 0.025), and evidence of outward remodeling with high shear (P = 0.007). Low shear immediately up-regulated TNF-α expression ∼50 fold (P < 0.001) at d1. Conversely, high shear-induced delayed and sustained TNF-α expression (22-fold at d7, P = 0.012; 23-fold at d14, P = 0.007). Both low and high shear gradually induced IL-10 expression (P = 0.002 and P = 0.004, respectively). Neither short-term (5-day) nor long-term (14-day) blockage of TNF-α signaling resulted in treatment-induced changes in the remodeling of low- or high-shear arteries.CONCLUSIONSShear stress differentially and temporally regulates TNF-α expression in remodeling large arteries. However, TNF-α blockage did not substantially impact the final shear-induced morphology, suggesting that large arteries can remodel in response to flow perturbations independent of TNF-α signaling.