Smoking increases tissue factor expression in atherosclerotic plaques: implications for plaque thrombogenicity.
BACKGROUND
Smoking increases the risk of atherothrombotic events. To determine whether smoking influences plaque thrombogenicity, we examined the effect of cigarette smoking and aspirin use on tissue factor (TF) expression in atherosclerotic plaques.


RESULTS
A total of 23 apoE-/- mice were exposed to cigarette smoke with (n=9) or without (n=14) aspirin treatment. Eleven mice who were exposed to filtered room air served as controls. Aortic root plaques of mice exposed to smoke had higher immunoreactivity for TF (14+/-4% versus 6.4+/-3%; P=0.0005), vascular cell adhesion molecule-1 (15+/-4% versus 5+/-2%; P=0.002), and macrophages (16+/-5% versus 6+/-2%; P=0.002) compared with nonsmoking controls. Aspirin treatment attenuated smoking-induced changes in plaque composition. In human plaques obtained by carotid endarterectomy, TF immunoreactivity (8+/-5% versus 2+/-2%; P=0.0002) and activity (P=0. 03) were higher in the plaques from smokers (n=28) than those from nonsmokers (n=28). Aspirin use was associated with reduced TF expression in smokers (9+/-8% versus 3+/-4%; P=0.0017).


CONCLUSIONS
Our results suggest increased plaque TF expression and thrombogenicity as a novel mechanism for the increased risk of atherothrombotic events in smokers. Treatment with aspirin may reduce TF expression.
Matetzky
S
S
Atherosclerosis Research Center, Division of Cardiology and Department of Medicine, Cedars-Sinai Medical Center and University of California School of Medicine, Los Angeles, CA 90048, USA.
Tani
S
S
Kangavari
S
S
Dimayuga
P
P
Yano
J
J
Xu
H
H
Chyu
K Y
KY
Fishbein
M C
MC
Shah
P K
PK
Cercek
B
B
D000368:Aged; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology*; D001241:Aspirin / Q000627:therapeutic use; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects*; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013927:Thrombosis / Q000209:etiology
D001057:Apolipoproteins E; D013925:Thromboplastin; D001241:Aspirin