Enhanced expression of haemoglobin scavenger receptor in accumulated macrophages of culprit lesions in acute coronary syndromes.
Enhanced expression of haemoglobin scavenger receptor in accumulated macrophages of culprit lesions in acute coronary syndromes.
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DOI：
10.1093/eurheartj/ehp257
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发表时间：
2009-08
影响因子：
39.3
通讯作者：
K. Yunoki;T. Naruko;R. Komatsu;S. Ehara;N. Shirai;K. Sugioka;M. Nakagawa;Chizuko Kitabayashi;Y. Ikura;A. Itoh;K. Kusano;T. Ohe;K. Haze;A. Becker;M. Ueda
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文献类型：
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作者：
K. Yunoki;T. Naruko;R. Komatsu;S. Ehara;N. Shirai;K. Sugioka;M. Nakagawa;Chizuko Kitabayashi;Y. Ikura;A. Itoh;K. Kusano;T. Ohe;K. Haze;A. Becker;M. Ueda
目的有效清除细胞外血红蛋白（Hb）被认为可以限制全身性氧化血红素毒性，而氧化血红素毒性被认为是导致斑块不稳定的发病机制。我们使用74例稳定型心绞痛（SAP，n = 39）或不稳定型心绞痛（UAP，n = 35）患者的冠状动脉粥样硬化斑块切除术标本，以化学方法检测斑块内出血、4-HNE（4-羟基-2-壬烯醛）（脂质过氧化指标）和Hb清道夫受体（CD 163）之间的关系。方法和结果动脉粥样硬化切除术样本用抗血型糖蛋白A（红细胞膜特异性蛋白）、CD 31、4-HNE和CD 163的抗体染色。定量分析显示，UAP患者的血型糖蛋白A阳性面积、4-HNE阳性巨噬细胞评分和CD 163阳性巨噬细胞评分显著高于SAP患者（血型糖蛋白A，P < 0.0001; 4-HNE阳性巨噬细胞评分，P < 0.0001; CD 163阳性巨噬细胞评分，P < 0.0005）。血型糖蛋白A阳性面积百分比与CD 31阳性微血管数和4-HNE阳性巨噬细胞评分呈显著正相关（微血管，R = 0.59，P < 0.0001; 4-HNE，R = 0.59，P < 0.0001）。此外，CD 163阳性巨噬细胞评分与血型糖蛋白A阳性面积和4-HNE阳性巨噬细胞评分呈正相关（血型糖蛋白A，R = 0.58，P < 0.0001; 4-HNE，R = 0.53，P < 0.0001）。结论不稳定斑块出血、血红蛋白清道夫受体表达增强与脂质过氧化呈正相关。
AIMS Effective clearance of extracellular haemoglobin (Hb) is thought to limit systemic oxidative heme toxicity, which is presumed to contribute to the pathogenesis of plaque instability. We immunohistochemically examined the relationship between intraplaque haemorrhage, 4-HNE (4-hydroxy-2-nonenal), an index of lipid peroxidation, and the Hb scavenger receptor (CD163), using coronary atherectomy specimens from 74 patients with stable angina pectoris (SAP, n = 39) or unstable angina pectoris (UAP, n = 35). METHODS AND RESULTS Atherectomy samples were stained with antibodies against glycophorin A (a protein specific to erythrocyte membranes), CD31, 4-HNE, and CD163. Quantitative analysis demonstrated that glycophorin A-positive areas, 4-HNE-positive macrophage score, and CD163-positive macrophage score in UAP patients were significantly higher (glycophorin A, P < 0.0001; 4-HNE-positive macrophage score, P < 0.0001; CD163-positive macrophage score, P < 0.0005) than in SAP patients. The percentage of the glycophorin A-positive area showed a significant positive correlation with the number of CD31-positive microvessels and the 4-HNE-positive macrophage score (microvessels, R = 0.59, P < 0.0001; 4-HNE, R = 0.59, P < 0.0001). Moreover, the CD163-positive macrophage score was positively correlated with glycophorin A-positive area and the 4-HNE-positive macrophage score (glycophorin A, R = 0.58, P < 0.0001; 4-HNE, R = 0.53, P < 0.0001). CONCLUSION These findings suggest a positive association among intraplaque haemorrhage, enhanced expression of Hb scavenger receptor, and lipid peroxidation in human unstable plaques.