Nicotine modulation of apoptosis in human coronary artery endothelial cells.

It has been recently reported that nicotine, the addictive component of tobacco, is an important modulator at the level of immune cell apoptosis or programmed cell death. Apoptosis is a process that helps maintain the homeostasis of the vascular endothelium and vascular smooth muscle cells, and alteration of the apoptotic process has been associated with cardiovascular diseases. The present study examined the effects and the mechanisms of action of nicotine on apoptosis in human coronary artery endothelial cells (HCAECs). Cultured HCAECs were treated with nicotine at a concentration that correlates with the tissue level of smokers (1 microg/ml), concurrently with tumor necrosis factor-alpha (TNF-alpha) and dexamethasone to induce apoptosis. The data showed that nicotine significantly inhibited apoptosis in HCAECs, as verified by the decreased expression level of active caspases compared to cells treated with the apoptosis inducers alone. This decrease was blocked by the addition of d-tubocurarine chloride (d-TC), a general nicotinic receptor antagonist, providing evidence that this action of nicotine was receptor-mediated. The findings were further confirmed by TUNEL assay for DNA fragmentation, a biochemical marker of apoptosis. This action of nicotine on apoptosis in human coronary artery endothelial cells suggests that nicotine may have an impact on cardiovascular pathology and atherogenesis.