The Phenotype of Infiltrating Macrophages Influences Arteriosclerotic Plaque Vulnerability in the Carotid Artery
The Phenotype of Infiltrating Macrophages Influences Arteriosclerotic Plaque Vulnerability in the Carotid Artery
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DOI：
10.1016/j.jstrokecerebrovasdis.2012.11.020
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发表时间：
2013-10-01
影响因子：
2.5
通讯作者：
Atsumi, Tatsuya
中科院分区：
文献类型：
--
作者：
Cho, Kyu Yong;Miyoshi, Hideaki;Atsumi, Tatsuya
背景：在动脉粥样硬化斑块中发现了促炎（M1）巨噬细胞和抗炎（M2）巨噬细胞。虽然这些巨噬细胞被推测与斑块脆弱性有关，但调查这种关系的研究有限。因此，我们研究了巨噬细胞表型（M1与M2）与斑块易损性和临床事件之间的关系。方法：接受颈动脉内膜切除术的患者在术前接受颈动脉超声检查。通过免疫组织化学、蛋白质印迹和实时聚合酶链反应研究处理噬菌斑进行分析。从病历中获得病史和临床数据。结果如下：患者分为2组：急性缺血发作（有症状，n = 31）和无症状（无症状，n = 34）。超声分析显示，有症状组的斑块易损性更大（P = 0.033;卡方检验）。免疫组化显示，有症状组的斑块具有更高浓度的M1巨噬细胞（CD 68-，CD 11 c-阳性），而无症状组的斑块具有更多的M2巨噬细胞（CD 163-阳性）。这一观察结果得到了Western印迹法的证实。实时聚合酶链反应研究表明，症状组斑块的M1标志物CD 68和CD 11 c，以及单核细胞趋化蛋白-1，白细胞介素-6和基质金属蛋白酶-9的表达增加。此外，更多的M1巨噬细胞在不稳定斑块中表达，而更多的M2巨噬细胞在稳定斑块中表达。结论：我们的数据显示，动脉粥样硬化斑块中M1巨噬细胞含量与缺血性卒中的临床发病率和炎症或纤维蛋白溶解增加相关。我们还展示了使用超声评估斑块易损性的益处。
Background: Proinflammatory (M1) macrophages and anti-inflammatory (M2) macrophages have been identified in atherosclerotic plaques. While these macrophages have been speculated to be related to plaque vulnerability, there are limited studies investigating this relationship. Therefore, we examined the association between macrophage phenotype (M1 versus M2) and plaque vulnerability and clinical events. Methods: Patients undergoing carotid endarterectomy received an ultrasound of the carotid artery before surgery. Plaques were processed for analysis by immunohistochemistry, Western blotting, and real-time polymerase chain reaction studies. Medical history and clinical data were obtained from medical records. Results: Patients were divided into 2 groups: those suffering from acute ischemic attack (symptomatic, n = 31) and those that did not present with symptoms (asymptomatic, n = 34). Ultrasound analysis revealed that plaque vulnerability was greater in the symptomatic group (P = .033; Chi-square test). Immunohistochemistry revealed that plaques from the symptomatic group had a greater concentration of M1 macrophages (CD68-, CD11c-positive) while plaques from the asymptomatic group had more M2 macrophages (CD163-positive). This observation was confirmed by Western blotting. Characterization by real-time polymerase chain reaction studies revealed that plaques from the symptomatic group had increased expression of the M1 markers CD68 and CD11c, as well as monocyte chemoattractive protein-1, interleukin-6, and matrix metalloproteinase-9. In addition, more M1 macrophages expressed in unstable plaques were defined by ultrasound analysis, while more M2 macrophages were expressed in stable plaques. Conclusions: Our data show that M1 macrophage content of atherosclerotic plaques is associated with clinical incidence of ischemic stroke and increased inflammation or fibrinolysis. We also show the benefits of using ultrasound to evaluate vulnerability in the plaques.