Disruption of vascular endothelial homeostasis by tobacco smoke: impact on atherosclerosis.

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 37 degrees C 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.