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从人动脉粥样硬化斑块中分离出的微粒的细胞起源和血栓形成活性。

Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques.

作者信息

Leroyer Aurélie S, Isobe Hirotaka, Lesèche Guy, Castier Yves, Wassef Michel, Mallat Ziad, Binder Bernd R, Tedgui Alain, Boulanger Chantal M

机构信息

INSERM Cardiovascular Research Center Lariboisière, Paris, France.

出版信息

J Am Coll Cardiol. 2007 Feb 20;49(7):772-7. doi: 10.1016/j.jacc.2006.10.053. Epub 2007 Feb 5.

DOI:10.1016/j.jacc.2006.10.053
PMID:17306706
Abstract

OBJECTIVES

In this study, we evaluated the cellular origins and thrombogenic potential of microparticles.

BACKGROUND

Human atherosclerotic plaques contain submicron vesicles (microparticles) released during cell activation or apoptosis.

METHODS

Microparticles were purified from plaques and platelet-free plasma from 26 patients undergoing carotid endarterectomy. Flow cytometry analysis revealed the presence of large amounts of microparticles in plaques but not in healthy vessels.

RESULTS

Most plaque microparticles originated from leukocytes, of which 29 +/- 5% were macrophages, 15 +/- 3% lymphocytes, and 8 +/- 1% granulocytes. Plaques microparticles also derived from erythrocytes (27 +/- 4%), smooth muscle (13 +/- 4%) and endothelial cells (8 +/- 2%), but not from platelets. Plaques from asymptomatic and symptomatic patients showed no differences in microparticle origins. Microparticles were at least 200-fold more concentrated in plaque than in plasma. Plasma microparticles were primarily platelet-derived in contrast with those of plaque and showed no smooth muscle cell origin. Both plaque and plasma microparticles exposed tissue factor and generated thrombin, but this activity was twice as high in microparticles isolated from plaques, reflecting the thrombogenic contribution of the individual classes of microparticles.

CONCLUSIONS

These results demonstrate that microparticles are more abundant and more thrombogenic in human atherosclerotic plaques than in plasma. The different cellular origins of plaque and plasma microparticles might explain the increased thrombogenic activity of plaque microparticles.

摘要

目的

在本研究中,我们评估了微粒的细胞起源和血栓形成潜力。

背景

人类动脉粥样硬化斑块包含在细胞活化或凋亡过程中释放的亚微米级囊泡(微粒)。

方法

从26例行颈动脉内膜切除术患者的斑块和无血小板血浆中纯化微粒。流式细胞术分析显示斑块中存在大量微粒,而健康血管中不存在。

结果

大多数斑块微粒起源于白细胞,其中29±5%为巨噬细胞,15±3%为淋巴细胞,8±1%为粒细胞。斑块微粒也来源于红细胞(27±4%)、平滑肌(13±4%)和内皮细胞(8±2%),但并非来源于血小板。无症状和有症状患者的斑块在微粒起源方面无差异。微粒在斑块中的浓度至少比血浆高200倍。与斑块微粒相比,血浆微粒主要来源于血小板,且未显示出平滑肌细胞起源。斑块和血浆微粒均暴露组织因子并产生凝血酶,但从斑块中分离出的微粒的这种活性高两倍,这反映了各类微粒的血栓形成作用。

结论

这些结果表明,人类动脉粥样硬化斑块中的微粒比血浆中更丰富且更具血栓形成性。斑块和血浆微粒的不同细胞起源可能解释了斑块微粒血栓形成活性增加的原因。

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