Circulating monocytes mirror the imbalance in TF and TFPI expression in carotid atherosclerotic plaques with lipid-rich and calcified morphology
Circulating monocytes mirror the imbalance in TF and TFPI expression in carotid atherosclerotic plaques with lipid-rich and calcified morphology
复制标题
DOI：
10.1016/j.thromres.2011.11.044
复制
发表时间：
2012-04-01
影响因子：
7.5
通讯作者：
Hansen, John-Bjarne
中科院分区：
文献类型：
--
作者：
Basavaraj, Manjunath Goolyam;Sovershaev, Mikhail A.;Hansen, John-Bjarne
背景：动脉粥样硬化斑块的血栓形成性在很大程度上取决于斑块形态及其组织因子（TF）和组织因子途径抑制剂（TFPI）的含量。斑块的形态组成（富含脂质或钙化）与循环血液单核细胞和斑块内TF和TFPI的表达之间的关系尚未确定。目的：探讨颈动脉粥样硬化斑块的富脂（回声）或钙化（回声）形态是否与循环血液单核细胞和颈动脉粥样硬化斑块内TF和TFPI表达差异有关。方法：我们研究了无症状的颈动脉斑块（n=20）有回声（n=20）或无回声（n=20）的颈动脉斑块，或无颈动脉粥样硬化的对照组（n=20）的单核细胞TF和TFPI mRNA和蛋白表达水平及其与动脉粥样硬化传统危险因素的关系。对有症状患者的钙化或富含脂质的颈动脉斑块切片进行TF和TFPI抗原表达评估。结果：有回声斑块或无颈动脉粥样硬化的对照组获得的单核细胞的TF和TFPI表面表现、表面TF/TFPI比率和TF活性均高于有回声斑块的受试者。多元回归分析显示，血清apoA1与单核细胞表面TF抗原表达呈负相关（p=0.007），血清apoB与单核细胞表面TFPI表达呈正相关（p=0.028）。与钙化病变相比，富脂颈动脉斑块切片的TF和TFPI抗原含量分别高出2.5倍和1.5倍，TF/TFPI比值也更高。结论：我们的研究结果表明，无症状的高脂颈动脉粥样硬化患者的循环单核细胞表达TF和TFPI之间的不平衡，这与从有症状患者获得的晚期颈动脉粥样硬化斑块中发现的变化一致。(C) 2011 Elsevier Ltd.版权所有。
Background: Thrombogenicity of atherosclerotic plaque largely depends on plaque morphology and their content of tissue factor (TF) and tissue factor pathway inhibitor (TFPI). The relationship between morphological composition of plaque (lipid-rich or calcified) and expression of TF and TFPI in circulating blood monocytes and within the plaques is not characterized.Objective: To investigate whether lipid-rich (echolucent) or calcified (echogenic) morphology of carotid atherosclerotic plaques is associated with differences in TF and TFPI expression in circulating blood monocytes and within carotid atherosclerotic plaques.Methods: We studied levels of monocyte TF and TFPI mRNA and protein expression and association with traditional risk factors for atherosclerosis in asymptomatic subjects with echolucent (n=20) or echogenic (n=20) carotid plaques, or controls without carotid atherosclerosis (n=20) determined by ultrasonography. Sections of calcified or lipid-rich carotid plaques obtained from symptomatic patients were assessed for TF and TFPI antigen expression.Results: TF and TFPI surface presentation, surface TF/TFPI ratio, and TF activity were higher in monocytes obtained from subjects with echolucent than with echogenic plaques or controls without carotid atherosclerosis. Multiple regression analyses revealed inverse association between serum apoA1 and monocyte surface TF antigen expression (p=0.007), and positive association between serum apoB and monocyte surface TFPI expression (p=0.028). Sections from lipid-rich carotid plaques contained 2.5-fold more TF and 1.5-fold more TFPI antigens relative to calcified lesions, also yielding a higher TF/TFPI ratio.Conclusions: Our findings indicate that circulating monocytes of asymptomatic individuals with echolucent lipid-rich carotid atherosclerosis express an imbalance between TF and TFPI expression cohering with changes found within advanced carotid atherosclerotic plaques obtained from symptomatic patients. (C) 2011 Elsevier Ltd. All rights reserved.