Enhanced TLR4 endothelial cell immunohistochemical expression in symptomatic carotid atherosclerotic plaques.
OBJECTIVE
Toll-like receptor-4 (TLR4) has been linked to the pathogenesis of atherosclerosis. Carotid atheroma endothelial cells (ECs) express TLR4, nevertheless correlations with cerebrovascular symptomatology, epidemiological and clinical variables remain unresolved.


METHODS
Carotid atherosclerotic plaques were obtained by standard carotid endarterectomy from 157 patients with carotid artery disease (84 asymptomatic - Group A, 73 symptomatic - Group B). TLR4 expression was detected by immunohistochemistry and TLR4 positivity, overexpression and intensity of immunostaining in ECs were correlated with cerebrovascular symptomatology, epidemiological and clinical variables.


RESULTS
A significant association was found between TLR4 positivity in ECs and the occurrence of any cerebrovascular event (overall response (OR): 2.85, 95% CI 1.33 - 6.11, p = 0.009). TLR4 overexpression and staining intensity in ECs were both significantly enhanced in symptomatic patients (p < 0.0001 and p = 0.003, respectively). These associations were stronger for the occurrence of a major cerebrovascular accident (CVA) compared with a transient ischemic attack (TIA) or amaurosis fugax. TLR4 expression in ECs was less prominent in statin users (OR: 0.25, 95%CI 0.1 - 0.58, p = 0.001], while it was enhanced in restenotic plaques compared with primary atherosclerotic lesions (p = 0.012).


CONCLUSIONS
TLR4 expression in ECs of carotid atheroma was enhanced in symptomatic patients with most commonly 'unstable' - 'more prone to rupture' carotid plaques.
Katsargyris
Athanasios
A
National and Kapodistrian University of Athens, School of Medicine, LAIKON Hospital, Vascular Division, 1st Department of Surgery, Goudi, GR11527, Athens, Greece.
Theocharis
Stamatios E
SE
Tsiodras
Sotirios
S
Giaginis
Konstantinos
K
Bastounis
Elias
E
Klonaris
Chris
C
D000368:Aged; D020757:Amaurosis Fugax / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D002097:C-Reactive Protein / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology*; D016893:Carotid Stenosis / Q000378:metabolism* / Q000473:pathology*; D016894:Endarterectomy, Carotid; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006083:Graft Occlusion, Vascular / Q000188:drug therapy / Q000453:epidemiology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism; D008297:Male; D020521:Stroke / Q000378:metabolism; D013927:Thrombosis / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000925:Anticoagulants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D006710:Homocysteine; D002097:C-Reactive Protein