Enhanced TLR4 endothelial cell immunohistochemical expression in symptomatic carotid atherosclerotic plaques

Background and Purpose: 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 = 0.0011, 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.