Regulation of low shear flow-induced HAEC VCAM-1 expression and monocyte adhesion
Regulation of low shear flow-induced HAEC VCAM-1 expression and monocyte adhesion
复制标题
DOI：
10.1152/ajpcell.1999.276.5.c1100
复制
发表时间：
1999-05-01
影响因子：
5.5
通讯作者：
Sprague, EA
中科院分区：
文献类型：
--
作者：
Mohan, S;Mohan, N;Sprague, EA
我们最近报道，人主动脉内皮细胞（HAEC）长期暴露于低切应力流动模式与转录调节因子核因子-κ B（NF-κ B）的活化形式的持续增加有关。在这里，我们调查的假设，即低剪切诱导的NF-κ B B的激活是负责增强血管细胞粘附分子（VCAM-1）的表达，导致增强内皮细胞-单核细胞（EC-Mn）粘附，这种激活是依赖于细胞内氧化剂的活性。在暴露于低剪切力（2 dyn/cm（2））6小时之前，HAEC与或不与抗氧化剂吡咯烷二硫代氨基甲酸酯（PDTC）或N-乙酰-L-半胱氨酸（NAC）预孵育。PDTC强烈抑制低剪切诱导的NF-κ B B活化、VCAM-1表达和EC-Mn粘附。NAC对低剪切诱导的VCAM-1表达和EC-Mn粘附有积极作用，但仅轻微下调NF-κ B B活化。然而，PDTC和NAC均阻断了苦参碱诱导的NF-κ B活化和VCAM-1表达。这些数据表明，NF-κ B B在低剪切诱导的VCAM-1表达中起关键作用，并且介导低剪切诱导的EC-Mn粘附的途径和精氨酸诱导的EC-Mn粘附可能受到差异调节。
We recently reported that prolonged exposure of human aortic endothelial cells (HAEC) to low shear stress flow patterns is associated with a sustained increase in the activated form of the transcriptional regulator nuclear factor-kappa B (NF-kappa B). Here we investigate the hypothesis that low shear-induced activation of NF-kappa B is responsible for enhanced expression of vascular cell adhesion molecule (VCAM-1) resulting in augmented endothelial cell-monocyte (EC-Mn) adhesion and that this activation is dependent on intracellular oxidant activity. Before exposure to low shear (2 dyn/cm(2)) for 6 h, HAEC were preincubated with or without the antioxidants pyrrolidine dithiocarbamate (PDTC) or N-acetyl-L-cysteine (NAC). PDTC strongly inhibited low shear-induced activation of NF-kappa B, expression of VCAM-1, and EC-Mn adhesion. Paradoxically, NAC exerted a positive effect on low shear-induced VCAM-1 expression and EC-Mn adhesion and only slightly downregulated NF-kappa B activation. However, cytokine-induced NF-kappa B activation and VCAM-1 expression are blocked by both PDTC and NAC. These data suggest that NF-kappa B plays a key role in low shear-induced VCAM-1 expression and that pathways mediating low shear- and cytokine-induced EC-Mn adhesion may be differentially regulated.