Early Atherosclerosis Exhibits an Enhanced Procoagulant State
Early Atherosclerosis Exhibits an Enhanced Procoagulant State
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DOI：
10.1161/circulationaha.109.907121
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发表时间：
2010-08-24
期刊：
影响因子：
37.8
通讯作者：
Spronk, Henri M. H.
中科院分区：
文献类型：
--
作者：
Borissoff, Julian Ilcheff;Heeneman, Sylvia;Spronk, Henri M. H.
凝血酶在体内的产生可能在调节动脉粥样硬化进展中起重要作用。在本研究中，我们第一次检查的活动和存在的相关凝血蛋白的进展atherosclerosis.Methods和Results-Both早期和稳定的先进的动脉粥样硬化病变进行了收集成对从每个人（n=27）在尸检。从总斑块和分离的斑块层制备组织匀浆，其中测定因子（F）II、X和XII以及组织因子的活性。微阵列分析，以阐明当地的信使RNA合成的凝血蛋白。将每个标本的一部分石蜡包埋，并使用商业抗体对组织切片进行多种凝血标志物的化学染色。数据表示为中位数（四分位距[IQR]）。组织因子、FIB、FX和FXII活性在早期动脉粥样硬化病变中显著高于稳定晚期动脉粥样硬化病变。内源性凝血酶潜能和凝血酶-抗凝血酶复合物值巩固了早期动脉粥样硬化病变的促凝血特征（内源性凝血酶潜能，1240 nmol/L.min [IQR，1173至1311];凝血酶-抗凝血酶复合物，1045 ng/mg [IQR，842.6 - 1376]）与稳定的晚期动脉粥样硬化病变（内源性凝血酶潜能，782 nmol/L.min [IQR，0 - 1151];凝血酶-抗凝血酶复合物，718.4 ng/mg [IQR，508.6 - 1151]）。组织因子、FVII和FX与巨噬细胞和平滑肌细胞共定位。此外，多种促凝血和抗凝蛋白酶的免疫组织化学映射到各个位置的动脉粥样硬化血管壁在早期和晚期atherosclerosis stages.Conclusions-This研究表明，早期动脉粥样硬化斑块的促凝血状态增强相比，先进的阶段斑块，这可能提供新的见解凝血的作用动脉粥样硬化斑块进展。（循环。2010;122：821-830）。
Background-Thrombin generation in vivo may be important in regulating atherosclerotic progression. In the present study, we examined for the first time the activity and presence of relevant coagulation proteins in relation to the progression of atherosclerosis.Methods and Results-Both early and stable advanced atherosclerotic lesions were collected pairwise from each individual (n=27) during autopsy. Tissue homogenates were prepared from both total plaques and isolated plaque layers, in which the activity of factors (F) II, X, and XII and tissue factor was determined. Microarray analysis was implemented to elucidate local messenger RNA synthesis of coagulation proteins. Part of each specimen was paraffin embedded, and histological sections were immunohistochemically stained for multiple coagulation markers with the use of commercial antibodies. Data are expressed as median (interquartile range [IQR]). Tissue factor, FII, FX, and FXII activities were significantly higher in early atherosclerotic lesions than in stable advanced atherosclerotic lesions. Endogenous thrombin potential and thrombin-antithrombin complex values consolidated a procoagulant profile of early atherosclerotic lesions (endogenous thrombin potential, 1240 nmol/L.min [IQR, 1173 to 1311]; thrombin-antithrombin complex, 1045 ng/mg [IQR, 842.6 to 1376]) versus stable advanced atherosclerotic lesions (endogenous thrombin potential, 782 nmol/L.min [IQR, 0 to 1151]; thrombin-antithrombin complex, 718.4 ng/mg [IQR, 508.6 to 1151]). Tissue factor, FVII, and FX colocalized with macrophages and smooth muscle cells. In addition, multiple procoagulant and anticoagulant proteases were immunohistochemically mapped to various locations throughout the atherosclerotic vessel wall in both early and advanced atherosclerotic stages.Conclusions-This study shows an enhanced procoagulant state of early-stage atherosclerotic plaques compared with advanced-stage plaques, which may provide novel insights into the role of coagulation during atherosclerotic plaque progression. (Circulation. 2010;122:821-830.)