Resveratrol attenuates TNF-α-induced activation of coronary arterial endothelial cells:: role of NF-kB inhibition
Resveratrol attenuates TNF-α-induced activation of coronary arterial endothelial cells:: role of NF-kB inhibition
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DOI：
10.1152/ajpheart.00340.2006
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发表时间：
2006-10-01
影响因子：
4.8
通讯作者：
Ungvari, Zoltan
中科院分区：
文献类型：
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作者：
Csiszar, Anna;Smith, Kira;Ungvari, Zoltan
白藜芦醇减弱TNF-α诱导的冠状动脉内皮细胞活化：NF-κ B抑制的作用Am J Physiol Heart Circ Physiol 291：H1694-H1699，2006; doi：10.1152/ajpheart. 00340.2006.流行病学研究表明，富含白藜芦醇的地中海饮食与降低冠状动脉疾病的风险有关。然而，白藜芦醇发挥其心脏保护作用的机制还不完全清楚。由于TNF-α诱导的内皮细胞活化和血管炎症在血管老化和动脉粥样硬化形成中起关键作用，我们评估白藜芦醇是否抑制TNF-α诱导的人冠状动脉内皮细胞（HCAECs）信号转导。我们发现TNF-α显著增加单核细胞THP-1细胞对HCAEC的增殖，这种作用可以被白藜芦醇和NF-κ B抑制剂吡咯烷二硫代氨基甲酸酯预处理抑制。以前，我们发现TNF-α激活NAD（P）H氧化酶，我们最近的数据表明，TNF-α诱导的内皮激活被NAD（P）H氧化酶抑制剂夹竹桃苷或过氧化氢酶加SOD阻止。白藜芦醇还能抑制H_2O_2诱导的单核细胞凋亡。使用报告基因分析，我们发现，在HCAEC中，TNF-α显著增加NF-κ B活性，这可以被白藜芦醇（10（-6）mol/l时抑制> 50%）和吡咯烷二硫代氨基甲酸酯抑制。白藜芦醇还抑制TNF-α诱导的，NF-κ B驱动的荧光素酶表达与报告基因构建体电穿孔的大鼠睾丸。在TNF-α处理的HCAEC中，白藜芦醇（亚微摩尔范围）显著减弱了NF-κ B依赖性炎症标记物诱导型一氧化氮合酶、IL-6、骨形态发生蛋白-2、ICAM-1和VCAM的表达。因此，营养相关浓度的白藜芦醇抑制TNF-α诱导的NF-κ B活化和炎性基因表达，并减弱单核细胞对HCAEC的粘附。我们认为，白藜芦醇的这些抗炎作用至少部分是其心脏保护作用的原因。
Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells: role of NF-kappa B inhibition. Am J Physiol Heart Circ Physiol 291: H1694-H1699, 2006; doi: 10.1152/ajpheart. 00340.2006. Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. However, the mechanisms by which resveratrol exerts its cardioprotective effects are not completely understood. Because TNF-alpha-induced endothelial activation and vascular inflammation play a critical role in vascular aging and atherogenesis, we evaluated whether resveratrol inhibits TNF-alpha-induced signal transduction in human coronary arterial endothelial cells (HCAECs). We found that TNF-alpha significantly increased adhesiveness of the monocytic THP-1 cells to HCAECs, an effect that could be inhibited by pretreatment with resveratrol and the NF-kappa B inhibitor pyrrolidine dithiocarbamate. Previously, we found that TNF-alpha activates NAD(P)H oxidases, and our recent data showed that TNF-alpha-induced endothelial activation was prevented by the NAD(P)H oxidase inhibitor apocynin or catalase plus SOD. Resveratrol also inhibited H2O2-induced monocyte adhesiveness. Using a reporter gene assay, we found that, in HCAECs, TNF-alpha significantly increased NF-kappa B activity, which could be inhibited by resveratrol (> 50% inhibition at 10(-6) mol/l) and pyrrolidine dithiocarbamate. Resveratrol also inhibited TNF-alpha-induced, NF-kappa B-driven luciferase expression in rat aortas electroporated with the reporter gene construct. In TNF-alpha-treated HCAECs, resveratrol (in the submicromolar range) significantly attenuated expression of NF-kappa B-dependent inflammatory markers inducible nitric oxide synthase, IL-6, bone morphogenetic protein-2, ICAM-1, and VCAM. Thus resveratrol at nutritionally relevant concentrations inhibits TNF-alpha-induced NF-kappa B activation and inflammatory gene expression and attenuates monocyte adhesiveness to HCAECs. We propose that these anti-inflammatory actions of resveratrol are responsible, at least in part, for its cardioprotective effects.