Colocalisation of intraplaque C reactive protein, complement, oxidised low density lipoprotein, and macrophages in stable and unstable angina and acute myocardial infarction

Colocalisation of intraplaque C reactive protein, complement, oxidised low density lipoprotein, and macrophages in stable and unstable angina and acute myocardial infarction
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DOI:
10.1136/jcp.2005.027235
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发表时间:
2006-02-01
影响因子:
3.4
通讯作者:
Piek, JJ
Piek, JJ
中科院分区:
医学3区
文献类型:
--
作者:
Meuwissen, M;van der Wal, AC;Piek, JJ

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背景:C反应蛋白(CRP)是一种重要的动脉粥样硬化性血管疾病的血清标志物,最近被报道在人类动脉粥样硬化斑块内活跃。目的:探讨不同冠状动脉综合征患者动脉粥样硬化切除术标本中巨噬细胞、CRP、膜攻击复合物C5b-9 (MAC)和氧化低密度脂蛋白(oxLDL)的同时存在。方法:对54例稳定型心绞痛(SA, n = 21)、不稳定型心绞痛(UA, n = 15)、心肌梗死(MI, n = 18)患者行冠脉病变定向冠状动脉粥样硬化切除术。冰冻切片的动脉粥样硬化斑块免疫组织化学染色单克隆抗体:抗cd68(巨噬细胞),抗5g4 (CRP), aE11 (MAC)和12E7 (oxLDL)。免疫阳性区域与纤维和新内膜组织、动脉粥样硬化和中膜的关系进行评估。定量分析采用系统随机抽样的图像细胞术(免疫阳性百分比/总组织面积)。结果:与SA相比,UA和MI患者动脉粥样硬化切除术标本中巨噬细胞、CRP、MAC和oxLDL同时存在的比例更高(p < 0.05)。定量分析显示,心肌梗死患者斑块中巨噬细胞的平均百分比(44%)明显高于UA (30%, p < 0.01)和SA (20%, p < 0.001)。与SA (12%, p < 0.05)相比,MI(25%)和UA(25%)的CRP平均百分比也显著高于SA (12%, p < 0.05)。结论:不稳定冠状动脉疾病患者斑块组织中高比例存在CRP、补体和oxLDL,表明这些替代标志物在动脉粥样硬化斑块内具有重要的促炎作用。这可能会增加斑块破裂和血栓形成的易感性,并带来后续的临床后遗症。
Background: C reactive protein (CRP), an important serum marker of atherosclerotic vascular disease, has recently been reported to be active inside human atherosclerotic plaques.Aims: To investigate the simultaneous presence of macrophages, CRP, membrane attack complex C5b-9 (MAC), and oxidised low density lipoprotein (oxLDL) in atherectomy specimens from patients with different coronary syndromes.Methods: In total, 54 patients with stable angina (SA; n = 21), unstable angina (UA; n = 15), and myocardial infarction (MI; n = 18) underwent directional coronary atherectomy for coronary lesions. Cryostat sections of atherosclerotic plaques were immunohistochemically stained with monoclonal antibodies: anti-CD68 (macrophages), anti-5G4 (CRP), aE11 (MAC), and 12E7 (oxLDL). Immunopositive areas were evaluated in relation to fibrous and neointima tissues, atheroma, and media. Quantitative analysis was performed using image cytometry with systematic random sampling ( percentage immunopositive/total tissue area).Results: Macrophages, CRP, MAC, and oxLDL were simultaneously present in a higher proportion of fibrous tissue and atheroma of atherectomy specimens from patients with UA and MI compared with SA (p < 0.05). Quantitative analysis showed significantly higher mean percentages of macrophages in plaques from patients with MI (44%) than UA (30%; p < 0.01) and SA (20%; p < 0.001). Significantly higher mean percentages of CRP were also seen in MI (25%) and UA (25%) compared with SA (12%; p < 0.05).Conclusions: The presence of CRP, complement, and oxLDL in a high proportion of plaque tissue from patients with unstable coronary artery disease implies that these surrogate markers have important proinflammatory effects inside atherosclerotic plaques. This may increase vulnerability to plaque rupture and thrombosis, with subsequent clinical sequelae.