A new research has revealed that nicotine, which is the major addictive substance in cigarette smoke, contributes to smokers’ higher risk of developing atherosclerosis, the primary cause of heart attacks.
Chi-Ming Hai from Brown University said the findings suggested that e-cigarettes, the battery-powered devices that deliver nicotine in steam without the carcinogenic agents of tobacco smoke, may not significantly reduce smokers’ risk for heart disease.
Dr. Hai’s research on human and rat vascular smooth muscle cells provides evidence of a link between nicotine and atherosclerosis.
In Dr. Hai’s experiments, nicotine appeared to drive the formation of a kind of cellular drill called podosome rosettes, which are members of the invadosome family, consisting of invadopodia, podosomes and podosome rosettes..
These specialized cell surface assemblies degrade and penetrate the tissue during cell invasion.
Dr. Hai subjected rat and primary human vascular smooth muscle cells to prolonged (six hours) nicotine treatment, enabling the cells to form podosome rosettes in response to Protein Kinase C (PKC) activation, which controls protein phosphorylation in signal transduction cascades.
The podosome rosettes set the scene for global extracellular matrix degradation and internalization. PKC activation alone, that is, without nicotine treatment, could induce the formation of podosomes in the rat muscle cells, accompanied by focal extracellular matrix degradation
Matrigel-coated transwell experiments indicated that nicotine treatment and PKC activation worked synergistically to enhance invasiveness in the primary human vascular smooth muscle cells.
Inclusion of alpha-bungarotoxin, a nicotinic acetylcholine receptor antagonist, or cycloheximide, a protein synthesis inhibitor, during nicotine treatment abolished nicotine-induced podosome rosette formation in the rat cells, suggesting that signalling through the nicotinic acetylcholine receptors and synthesis of new proteins are required for podosome rosette formation.
The study was presented at the American Society for Cell Biology Annual Meeting in New Orleans.