CHARACTERIZATION OF THE RELATIVE THROMBOGENICITY OF ATHEROSCLEROTIC PLAQUE COMPONENTS - IMPLICATIONS FOR CONSEQUENCES OF PLAQUE RUPTURE
CHARACTERIZATION OF THE RELATIVE THROMBOGENICITY OF ATHEROSCLEROTIC PLAQUE COMPONENTS - IMPLICATIONS FOR CONSEQUENCES OF PLAQUE RUPTURE
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DOI：
10.1016/0735-1097(94)90657-2
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发表时间：
1994-06-01
影响因子：
24
通讯作者：
BADIMON, L
中科院分区：
文献类型：
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作者：
FERNANDEZORTIZ, A;BADIMON, JJ;BADIMON, L
目的。本研究旨在确定暴露于流动血液中的人类动脉粥样硬化斑块的不同成分是否会导致不同程度的血栓形成。
背景。自发性或血管成形术诱导的斑块破裂后暴露的基质性质可能是决定不稳定斑块是迅速发展为闭塞性血栓还是持续为非闭塞性附壁血栓的一个因素。尽管观察数据表明斑块破裂是血栓形成的有力刺激因素，且暴露的胶原被认为在血栓形成中起主要作用，但人类动脉粥样硬化斑块不同成分的相对致血栓性尚未明确确定。
方法。我们研究了在富含泡沫细胞的基质（从脂肪条纹获取）、富含胶原的基质（从硬化斑块获取）、无胆固醇晶体的贫胶原基质（从纤维脂质斑块获取）、含有大量胆固醇晶体的粥样核心（从粥样斑块获取）以及尸检时取自人类主动脉的正常内膜片段上的血栓形成情况。将标本安装在置于体外体外灌注系统内的管状腔室中，并在高剪切率条件（1690秒⁻¹）下暴露于肝素化的猪血（平均[±标准误]活化部分凝血活酶时间比值为1.5 ± 0.04）中5分钟。通过测量铟标记的血小板和形态计量分析对血栓进行定量。在类似条件下，在体外系统中用肝素化的人血（2国际单位/毫升）灌注基质，并对血栓形成情况进行类似评估。
结果。在异源和同源系统中，粥样核心上的血栓形成量比其他基质（包括富含胶原的基质）多达6倍（p = 0.0001）。尽管粥样核心具有更不规则的暴露表面，且血栓形成往往随着粗糙度的增加而增加，但当根据粗糙度指数所定义的不规则程度对基质进行标准化时，粥样核心仍然是最具致血栓性的基质（p <0.002）。
结论。粥样核心是人类动脉粥样硬化斑块中最具致血栓性的成分。因此，由于其内容物的致血栓性增加，含有大量粥样核心的斑块在自发性或机械性诱导破裂后导致急性冠状动脉综合征的风险较高。
Objectives. The purpose of this study was to determine whether different components of human atherosclerotic plaques exposed to flowing blood resulted in different degrees of thrombus formation.Background. It is likely that the nature of the substrate exposed after spontaneous or angioplasty induced plaque rupture is one factor determining whether an unstable plaque proceeds rapidly to an occlusive thrombus or persists as a nonocclusive mural thrombus. Although observational data show that plaque rupture is a potent stimulus for thrombosis, and exposed collagen is suggested to have a predominant role in thrombosis, the relative thrombogenicity of different components of human atherosclerotic plaques is not well established.Methods. We investigated thrombus formation on foam cell rich matrix (obtained from fatty streaks), collagen-rich matrix (from sclerotic plaques), collagen poor matrix without cholesterol crystals (from fibrolipid plaques), atheromatous core with abundant cholesterol crystals (from atheromatous plaques) and segments of normal intima derived from human aortas at necropsy. Specimens were mounted in a tubular chamber placed within an ex vivo extracorporeal perfusion system and exposed to heparinized porcine blood (mean [+/-SEM] activated partial thromboplastin time ratio 1.5 +/- 0.04) for 5 min under high shear rate conditions (1,690 s(-1)). Thrombus was quantitated by measurement of indium-labeled platelets and morphometric analysis. Under similar conditions, substrates were perfused with heparinized human blood (2 IU/ml) in an in vitro system, and thrombus formation was similarly evaluated.Results. Thrombus formation on atheromatous core was up to sixfold greater than that on other substrates, including collagen rich matrix (p = 0.0001) in both heterologous and homologous systems. Although the atheromatous core had a more irregular exposed surface and thrombus formation tended to increase with increasing roughness, the atheromatous core remained the most thrombogenic substrate when the substrates were normalized by the degree of irregularity as defined by the roughness index (p 0.002).Conclusions. The atheromatous core is the most thrombogenic component of human atherosclerotic plaques. Therefore, plaques with a large atheromatous core content are at high risk of leading to acute coronary syndromes after spontaneous or mechanically induced rupture because of the increased thrombogenicity of their content.