Smoking Increases Tissue Factor Expression in Atherosclerotic Plaques

Abstract

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. Methods and 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.