Ribichini Flavio, Pugno Francesco, Ferrero Valeria, Bussolati Gianni, Feola Mauro, Russo Paolo, Di Mario Carlo, Colombo Antonio, Vassanelli Corrado
Catheterization Laboratory, Ospedale Maggiore della Carità, Universita' del Piemonte Orientale, Novara, Italy.
J Am Coll Cardiol. 2006 Mar 21;47(6):1143-9. doi: 10.1016/j.jacc.2005.12.022. Epub 2006 Feb 23.
The aim of this study was to determine the cellular localization of angiotensin I-converting enzyme (ACE) in the atherosclerotic plaque and its correlation with inflammation and cellular proliferation.
Angiotensin I-converting enzyme inhibitors reduce the incidence of vascular events; therefore, tissue ACE may play a determinant role in the pathophysiology of the atherosclerotic plaque.
Histology and immunocytochemistry of de novo coronary plaques retrieved with directional coronary atherectomy from 141 patients were analyzed: 87 with stable angina, 39 with subacute unstable angina, and 15 with acute unstable angina.
Compared with stable patients, unstable patients showed more thrombotic lesions (72% vs. 27%, p < 0.0001), smaller areas of fibrous plaque (2.3 +/- 1.2 mm2 vs. 2.8 +/- 1.1 mm2, p = 0.02), higher cellular proliferative score (0.78 +/- 0.9 vs. 0.27 +/- 0.6, p = 0.003), larger content of ACE-stained cells (26.3 +/- 23% vs. 12.6 +/- 15%, p = 0.005) and larger areas of inflammation as identified by CD68 immunostaining (29.5 +/- 22% vs. 20.2 +/- 19%, p = 0.02). A significant linear correlation was found between CD68- and ACE-stained areas (mm2) among unstable patients (r = 0.6, p = 0.0001), but it was absent among stable patients (r = 0.006, p = 0.9). Co-localization of ACE, CD68, and alpha-actin was confirmed by double immunostaining. Patients with Ki-67-positive staining as an index of cell proliferation showed also significantly larger areas of ACE immunoactivity (p = 0.004).
Our data demonstrate ACE immunoactivity in inflammatory and proliferative cells of coronary atherosclerotic plaques. In particular, patients with unstable angina showed larger areas of ACE immunoactive tissue and proliferating cells compared with stable patients. These observations support a role of the enzyme in the pathophysiology of coronary unstable plaques and suggest potentially different effects of ACE inhibitors according to clinical presentation.
本研究旨在确定血管紧张素I转换酶（ACE）在动脉粥样硬化斑块中的细胞定位及其与炎症和细胞增殖的相关性。
血管紧张素I转换酶抑制剂可降低血管事件的发生率；因此，组织ACE可能在动脉粥样硬化斑块的病理生理学中起决定性作用。
对141例患者经定向冠状动脉斑块旋切术获取的新鲜冠状动脉斑块进行组织学和免疫细胞化学分析：87例稳定型心绞痛患者，39例亚急性不稳定型心绞痛患者，15例急性不稳定型心绞痛患者。
与稳定型患者相比，不稳定型患者血栓形成病变更多（72%对27%，p<0.0001），纤维斑块面积更小（2.3±1.2mm²对2.8±1.1mm²，p=0.02），细胞增殖评分更高（0.78±0.9对0.27±0.6，p=0.003），ACE染色细胞含量更高（26.3±23%对12.6±15%，p=0.005），CD68免疫染色显示炎症面积更大（29.5±22%对20.2±19%，p=0.02）。在不稳定型患者中，CD68染色面积（mm²）与ACE染色面积之间存在显著线性相关性（r=0.6，p=0.0001），而在稳定型患者中不存在（r=0.006，p=0.9）。通过双重免疫染色证实了ACE、CD68和α-肌动蛋白的共定位。以Ki-67阳性染色作为细胞增殖指标的患者，其ACE免疫活性面积也显著更大（p=0.004）。
我们的数据表明ACE在冠状动脉粥样硬化斑块的炎症和增殖细胞中具有免疫活性。特别是，与稳定型患者相比，不稳定型心绞痛患者的ACE免疫活性组织和增殖细胞面积更大。这些观察结果支持该酶在冠状动脉不稳定斑块病理生理学中的作用，并提示根据临床表现，ACE抑制剂可能具有不同的作用效果。
