Expression of tissue factor in high-grade carotid artery stenosis: association with plaque destabilization.
OBJECTIVE
The procoagulant protein tissue factor (TF) has been implicated in thromboembolic complications associated with advanced atherosclerosis. In this study, we investigated whether TF expression in high-grade stenoses of the internal carotid artery (ICA) is associated with clinical features of plaque destabilization and addressed the relationship between TF expression and plaque inflammation.


METHODS
In 36 consecutive patients undergoing surgery for high-grade ICA stenosis, clinical evidence of plaque instability was provided by the recent occurrence of ischemic symptoms attributable to the stenosis and the detection of cerebral microembolism by means of transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. Endarterectomy specimens were stained immunocytochemically for TF expression as well as macrophage (CD68) and T cell (CD3) infiltration.


RESULTS
Morphologically, TF immunoreactivity was codistributed with plaque inflammation and predominantly localized to CD68+ macrophages. Accordingly, statistical analysis revealed a significant association of TF expression with plaque infiltration by macrophages (P<0.0001) and T cells (P=0.013). Plaques extensively stained for TF (median of TF+ total section area >40% in semiquantitative assessment) were more frequent in symptomatic (12/27) than in asymptomatic patients (1/9). Conversely, plaques exhibiting little TF expression (median of TF+ section area <20%) were more frequent in asymptomatic (3/9) than in symptomatic (1/27) patients (P=0.016). Likewise, we found a highly significant association of TF expression with the occurrence of cerebral microembolism (P=0.008).


CONCLUSIONS
Induction of TF at sites of plaque inflammation may play an important role in the destabilization of high-grade ICA stenosis.
Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany. jander@uni-duesseldorf.de
S
S
Jander
M
M
Sitzer
A
A
Wendt
M
M
Schroeter
M
M
Buchkremer
M
M
Siebler
W
W
Müller
W
W
Sandmann
G
G
Stoll
D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016893:Carotid Stenosis / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D016894:Endarterectomy, Carotid; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000175:diagnosis / Q000473:pathology; D020766:Intracranial Embolism / Q000175:diagnosis / Q000209:etiology; D002546:Ischemic Attack, Transient / Q000209:etiology; D008264:Macrophages / Q000473:pathology; D011446:Prospective Studies; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000473:pathology; D013925:Thromboplastin / Q000096:biosynthesis*; D017585:Ultrasonography, Doppler, Transcranial
D013925:Thromboplastin