National and Kapodistrian University of Athens, School of Medicine, LAIKON Hospital, Vascular Division, 1st Department of Surgery, Goudi, GR11527, Athens, Greece.
Expert Opin Ther Targets. 2010 Jan;14(1):1-10. doi: 10.1517/14728220903401294.
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.
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.
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).
TLR4 expression in ECs of carotid atheroma was enhanced in symptomatic patients with most commonly 'unstable' - 'more prone to rupture' carotid plaques.
Toll 样受体 4（TLR4）与动脉粥样硬化的发病机制有关。颈动脉粥样硬化斑块内皮细胞（ECs）表达 TLR4，然而与脑血管症状、流行病学和临床变量的相关性仍未解决。
通过标准颈动脉内膜切除术从 157 例颈动脉疾病患者（无症状 84 例-组 A，有症状 73 例-组 B）中获得颈动脉粥样硬化斑块。通过免疫组织化学检测 TLR4 表达，ECs 中 TLR4 阳性、过表达和免疫染色强度与脑血管症状、流行病学和临床变量相关。
发现 ECs 中 TLR4 阳性与任何脑血管事件的发生之间存在显著关联（总体反应（OR）：2.85，95%CI 1.33-6.11，p=0.009）。有症状患者的 ECs 中 TLR4 过表达和染色强度均显著增强（p<0.0001 和 p=0.003）。与短暂性脑缺血发作（TIA）或一过性黑矇相比，这些关联在主要脑血管意外（CVA）的发生中更为明显。他汀类药物使用者 ECs 中的 TLR4 表达较弱（OR：0.25，95%CI 0.1-0.58，p=0.001），而在再狭窄斑块中比原发性动脉粥样硬化病变中增强（p=0.012）。
颈动脉粥样硬化斑块中 ECs 的 TLR4 表达在有症状的患者中增强，这些患者的颈动脉斑块最常见的是“不稳定”-“更容易破裂”。
