Human Coronary Thrombus Formation Is Associated With Degree of Plaque Disruption and Expression of Tissue Factor and Hexokinase II
Human Coronary Thrombus Formation Is Associated With Degree of Plaque Disruption and Expression of Tissue Factor and Hexokinase II
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DOI：
10.1253/circj.cj-15-0394
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发表时间：
2015-11-01
影响因子：
3.3
通讯作者：
Asada, Yujiro
中科院分区：
文献类型：
--
作者：
Okuyama, Nozomi;Matsuda, Shuntaro;Asada, Yujiro
背景：动脉粥样硬化斑块的血栓形成性是影响血栓形成和急性心肌梗死（AMI）发病的关键因素。本研究的目的是确定参与血栓形成和AMI发病的血管因素。方法与结果：对40例致死性急性心肌梗死（AMI）和非心源性死亡（无症状斑块破裂）尸检时出现血栓的冠状动脉罪魁祸首病变进行组织学分析。AMI患者的冠状动脉血栓大小、血栓与管腔面积之比、斑块破裂长度、组织因子（TF）和己糖激酶(HK)-II免疫阳性区域均明显大于无症状斑块破裂患者。冠状动脉血栓大小与斑块破裂长度呈正相关（r=0.80），与TF （r=0.38）和HK-II （r=0.40）免疫阳性区域呈正相关。由于M1和M2巨噬细胞在症状斑块中均表达TF和HK-II，因此我们评估了M1和M2极化巨噬细胞中TF和HK-II的表达。与m1极化的THP-1巨噬细胞相比，M2-中TF表达升高，HK-II表达降低。抑制糖酵解部分通过缺氧诱导因子-1 α增强巨噬细胞中TF的表达。结论：斑块破坏程度、TF和HK-II的表达似乎是AMI发病的重要血管因素，极化巨噬细胞对血栓形成和糖代谢有明显的贡献。
Background: Atherosclerotic plaque thrombogenicity is a critical factor that affects thrombus formation and the onset of acute myocardial infarction (AMI). The aim of this study was to identify the vascular factors involved in thrombus formation and AMI onset.Methods and Results: Culprit lesions in 40 coronary arteries with thrombi at autopsy after lethal AMI and non-cardiac death (asymptomatic plaque disruption) were analyzed on histology. Thrombus size, ratio of thrombus to lumen area, length of plaque disruption, and immunopositive areas for tissue factor (TF) and hexokinase (HK)-II were significantly larger in coronary arteries with AMI than with asymptomatic plaque disruption. The size of coronary thrombus positively correlated with the length of plaque disruption (r=0.80) and with immunopositive areas for TF (r=0.38) and HK-II (r=0.40). Because both M1 and M2 macrophages express TF and HK-II in symptomatic plaques, we assessed TF and HK-II expression in M1- and M2-polarized macrophages. The expression of TF was increased and that of HK-II was decreased in M2-, compared with M1-polarized THP-1 macrophages. Inhibiting glycolysis enhanced TF expression in the macrophages partly via hypoxia inducible factor-1 alpha.Conclusions: The degree of plaque disruption and expression of TF and HK-II appear to be important vascular factors for AMI onset, and polarized macrophages make a distinct contribution to thrombogenicity and glucose metabolism.