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Nicotine drives cell invasion that contributes to plaque formation in coronary arteries
Date:12/15/2013

on 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.

Nicotinic acetylcholine receptors, which bind neurotransmitters, co-localized with other podosome markers (vinculin, PKC-alpha, and metalloproteinase-2) at podosomes and podosome rosettes in the rat cells.

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 signaling through the nicotinic acetylcholine receptors and synthesis of new proteins are required for podosome rosette formation.

Altogether the data from the studies of rat and primary human vascular smooth muscle cells suggest that nicotine enhances vascular smooth muscle cell invasion by activating synergistic mechanisms between the nicotinic acetylcholine receptor and PKC signaling.

According to Dr. Hai, a potential clinical implication of these findings is that replacing cigarette smoking by nicotine administration may not bring much benefit to lowering the risk of developing atherosclerosis. Still, Dr. Hai said that he believes that understanding the synergistic mechanisms between nicotinic acetylcholine receptor and PKC in vascular smooth muscle invasion may lead to new therapeutics for minimizing the damaging effects of nicotine on the vascular system.


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Contact: Cathy Yarbrough
cyarbrough@ascb.org
858-243-1814

John Fleischman
jfleischman@ascb.org

American Society for Cell Biology
Source:Eurekalert


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