Department of Nutrition and Dietetics, Harokopio University of Athens, 70 El Venizelou Ave, Athens, Greece.
Lipids Health Dis. 2014 Apr 23;13:70. doi: 10.1186/1476-511X-13-70.
Clusterin (CLU) /Apolipoprotein J is a protein biosensor of oxidative stress and inflammation, which is upregulated in many pathological processes including atherosclerosis. Previous studies have shown that in aortic tissue, CLU expression increases with atherosclerotic lesion progression and it has been coupled with vascular damage and coronary artery disease. A few studies enter into CLU and carotid atherosclerosis while the apolipoprotein's expression on human carotid tissue and its association with parameters related to the disease development has not been examined. The present study was designed to reveal the relationships between the degree of CLU immunolocalization on carotid artery and demographic characteristics, blood parameters and pharmacological treatment of patients underwent internal carotid artery endarterectomy.
CLU expression was detected by immunohistochemistry in 42 carotid endarterectomy specimens. Patients' serum levels of tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP) and classical parameters related to atherosclerosis such as lipid profile, as well as thrombosis related parameters such as fibrinogen, antithrombin III, protein C and protein S were determined. Demographic characteristics, smoking habits and the use of medications were recorded. Comparisons between groups were performed by students't-test and analysis of variance. Independent associations with CLU expression on carotid tissue were denoted by linear regression analysis.
CLU imuunolocalization was denser in smokers than in non-smokers (p = 0.041) while it was rarefied in specimens of patients on cropidogrel treatment (p = 0.045) compared to the rest not taking this medication. Clopidogrel intake was independent predictor of lower CLU expression on carotid artery (p =0.045). CLU was positively correlated with serum TNF-a concentration (r = 0.33, p = 0.040) that was independent predictor of higher expression of the apolipoprotein (p = 0.001). IL-6, hsCRP and classical parameters related to atherosclerosis and thrombosis were not associated with CLU immunolocalization.
Our study suggests that CLU expression on carotid artery is affected by TNF-alpha, cigarette smoking confirming its association with oxidative and cellular stress and anti-platelet medication reflecting the protective effects of such pharmacological treatment on vascular wall.
簇集蛋白（CLU）/载脂蛋白 J 是一种氧化应激和炎症的蛋白生物传感器，在包括动脉粥样硬化在内的许多病理过程中上调。先前的研究表明，在主动脉组织中，CLU 的表达随着动脉粥样硬化病变的进展而增加，并且与血管损伤和冠心病有关。一些研究涉及 CLU 和颈动脉粥样硬化，而载脂蛋白在人颈动脉组织中的表达及其与疾病发展相关参数的关系尚未被研究。本研究旨在揭示颈动脉粥样硬化患者的颈动脉组织中 CLU 免疫定位程度与人口统计学特征、血液参数和药物治疗之间的关系。
采用免疫组织化学方法检测 42 例颈动脉内膜切除术标本中 CLU 的表达。检测患者血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、高敏 C 反应蛋白（hsCRP）以及与动脉粥样硬化相关的经典参数，如血脂谱，以及与血栓形成相关的参数，如纤维蛋白原、抗凝血酶 III、蛋白 C 和蛋白 S。记录人口统计学特征、吸烟习惯和药物使用情况。组间比较采用学生 t 检验和方差分析。与颈动脉组织中 CLU 表达的独立相关性采用线性回归分析。
与不吸烟者相比，吸烟者的 CLU 免疫定位更密集（p=0.041），而服用氯吡格雷的患者标本中（p=0.045）CLU 免疫定位较其他未服用该药物的患者稀疏。氯吡格雷的摄入是颈动脉 CLU 表达降低的独立预测因子（p=0.045）。CLU 与血清 TNF-α浓度呈正相关（r=0.33，p=0.040），而 TNF-α是载脂蛋白高表达的独立预测因子（p=0.001）。IL-6、hsCRP 和与动脉粥样硬化和血栓形成相关的经典参数与 CLU 免疫定位无关。
我们的研究表明，颈动脉组织中 CLU 的表达受 TNF-α和吸烟的影响，这证实了其与氧化和细胞应激的关系，以及抗血小板药物的作用，反映了这种药物治疗对血管壁的保护作用。
