Disruption of vascular endothelial homeostasis by tobacco smoke - impact on atherosclerosis

Disruption of vascular endothelial homeostasis by tobacco smoke - impact on atherosclerosis
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DOI:
10.1096/fj.03-0312fje
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发表时间:
2003-10-01
期刊:
影响因子:
4.8
通讯作者:
Wick, G
Wick, G
中科院分区:
生物学2区
文献类型:
--
作者:
Bernhard, D;Pfister, G;Wick, G

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世界卫生组织(世卫组织)预测,到2020年,烟草将成为全世界最大的单一健康问题,估计每年将造成840万人死亡(http://www5.who.int/tobacco/)。虽然从医学的角度来看,吸烟对人体健康的影响是明确的,但令人惊讶的是,人们对烟草烟雾介导其灾难性影响的机制知之甚少。在这里,我们证明烟草烟雾显著改变血管内皮细胞和组织形态,导致内皮屏障功能在几分钟内丧失。内皮细胞长期暴露于烟草烟雾提取物中会引起坏死,从而引发血管壁的促炎状态。不含细胞的提取物在37℃下预孵育6小时导致活性完全丧失。此外,即使在提取物失去活性的情况下,内皮细胞也可以通过更换新鲜培养基来恢复。最后,我们发现n -乙酰半胱氨酸和他汀类药物抑制烟草烟雾的不良影响。
The World Health Organization (WHO) predicts that by 2020 tobacco will become the largest single health problem worldwide and will cause an estimated 8.4 million deaths annually (http://www5.who.int/tobacco/). Although the impact of smoking on human health is well defined from the medical point of view, surprisingly little is known about the mechanisms by which tobacco smoke mediates its disastrous effects. Here, we demonstrate that tobacco smoke dramatically changes vascular endothelial cell and tissue morphology, leading to a loss of endothelial barrier function within minutes. Long-term exposure of endothelial cells to tobacco smoke extracts induces necrosis that may trigger a pro-inflammatory status of the vessel wall. Pre-incubation of the extracts without cells for 6 h at 37degreesC led to a complete loss of activity. Further, the endothelium could be rescued by changing to fresh medium even at times when the extracts had lost their activity. Finally, we show that N-acetyl cysteine and statins inhibit the adverse tobacco smoke effects.