Early Atherosclerosis Exhibits an Enhanced Procoagulant State

被引：199

作者：

Borissoff, Julian Ilcheff ^{[1
]}

Heeneman, Sylvia ^{[2
]}

Kilinc, Evren ^{[1
]}

Kassak, Peter ^{[1
]}

Van Oerle, Rene ^{[1
]}

Winckers, Kristien ^{[1
,3
]}

Govers-Riemslag, Jose W. P. ^{[1
]}

Hamulyak, Karly ^{[4
]}

Hackeng, Tilman M. ^{[3
]}

Daemen, Mat J. A. P. ^{[2
]}

Ten Cate, Hugo ^{[1
]}

Spronk, Henri M. H. ^{[1
]}

机构：

[1] Maastricht Univ Med Ctr, Cardiovasc Res Inst Maastricht, Lab Clin Thrombosis & Hemostasis, Dept Internal Med, NL-6200 MD Maastricht, Netherlands

[2] Maastricht Univ Med Ctr, Cardiovasc Res Inst Maastricht, Dept Pathol, NL-6200 MD Maastricht, Netherlands

[3] Maastricht Univ Med Ctr, Cardiovasc Res Inst Maastricht, Dept Biochem, NL-6200 MD Maastricht, Netherlands

[4] Maastricht Univ Med Ctr, Cardiovasc Res Inst Maastricht, Div Hematol, Dept Internal Med, NL-6200 MD Maastricht, Netherlands

来源：

CIRCULATION | 2010年 / 122卷 / 08期

关键词：

atherosclerosis; hypercoagulability; immunohistochemistry; plaque; thrombosis; FACTOR PATHWAY INHIBITOR; CALIBRATED AUTOMATED THROMBOGRAM; PROTEASE-ACTIVATED RECEPTOR-1; TISSUE FACTOR; THROMBIN GENERATION; PLAQUE STABILITY; COAGULATION; INJURY; MICE; HYPERCOAGULABILITY;

D O I：

10.1161/CIRCULATIONAHA.109.907121

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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.)

引用

页码：821 / U145

页数：23

共 35 条

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Local inhibition of tissue factor reduces the thrombogenicity of disrupted human atherosclerotic plaques - Effects of tissue factor pathway inhibitor on plaque thrombogenicity under flow conditions [J].