Department of Cardiac Surgery, Harefield Hospital, Royal Brompton and Harefield Hospitals, Part of Guy's and St. Thomas' NHS Foundation Trust, London, UK.
Department of Vascular Surgery, University Hospital Centre Rijeka, Rijeka, Croatia, EU.
J Stroke Cerebrovasc Dis. 2022 Nov;31(11):106731. doi: 10.1016/j.jstrokecerebrovasdis.2022.106731. Epub 2022 Sep 5.
Matrix metalloproteinase-9 protein (MMP-9) and cyclooxygenase-2 (COX-2) proteins may have a role in remodelling of atherosclerotic plaques. We analysed and compared the radiological, histological and immunohistochemical characteristics of carotid atherosclerotic plaques between symptomatic and asymptomatic patients who underwent carotid endarterectomy (CEA).
This prospective single-blinded study included 31 patients (70 [64-75] years, 58% males, 42% symptomatic) who underwent CEA and a total of 155 carotid plaque sections that were analysed. Preoperative assessment and multimodality diagnostic imaging with magnetic resonance imaging (MRI) or computed tomography angiography (CTA), histological and immunohistochemical analyses of carotid plaques including the expression of MMP-9 and COX-2 proteins were performed.
Symptomatic and asymptomatic patients did not significantly differ in respect to preoperative characteristics. Unstable plaques were detected in 12/13 (92.3%, p = 0.020) symptomatic patients using MRI or CTA. There was no perioperative mortality and perioperative outcomes were comparable in both groups. A significantly higher expression of MMP-9 in macrophages was observed among symptomatic patients (p = 0.020). ROC curve analysis showed statistically significant associations of both the higher intensity of COX-2 staining in CD68 PG-M1 positive macrophages (area under the curve [AUC]=0.701, p = 0.014) and higher MVD (AUC=0.821, p < 0.001) within the plaque with cerebrovascular symptoms. The expression of COX-2 and the intensity of COX-2 staining in macrophages within the unstable carotid plaques detected by preoperative MRI or CTA were significantly higher (76.1% vs. 40.0%, p = 0.038; 76.2% vs. 30.0%, p = 0.01, respectively).
Advanced non-invasive multimodality diagnostic imaging including MRI or CTA is reliable in differentiating unstable from stable carotid plaques. High expression of MMP-9 and COX-2 in macrophages within the symptomatic plaque is associated with increased risk of cerebrovascular complications.
This study has been registered at the ISRCTN registry (ID ISRCTN46536832), isrctn.org Identifier: https://www.isrctn.com/ISRCTN46536832.
基质金属蛋白酶-9 蛋白（MMP-9）和环氧化酶-2（COX-2）蛋白可能在动脉粥样硬化斑块的重塑中发挥作用。我们分析并比较了接受颈动脉内膜切除术（CEA）的有症状和无症状患者颈动脉粥样硬化斑块的影像学、组织学和免疫组织化学特征。
这项前瞻性单盲研究纳入了 31 名患者（70 岁[64-75]岁，58%为男性，42%有症状），他们接受了 CEA，并对总共 155 个颈动脉斑块节段进行了分析。进行了术前评估和多模态诊断成像，包括磁共振成像（MRI）或计算机断层血管造影（CTA），以及颈动脉斑块的组织学和免疫组织化学分析，包括 MMP-9 和 COX-2 蛋白的表达。
有症状和无症状患者在术前特征方面无显著差异。使用 MRI 或 CTA 在 13 名有症状患者中的 12 名（92.3%，p=0.020）中检测到不稳定斑块。两组围手术期均无死亡，围手术期结局相似。在有症状患者中，巨噬细胞中 MMP-9 的表达明显更高（p=0.020）。ROC 曲线分析显示，斑块内 COX-2 染色强度较高的巨噬细胞（曲线下面积[AUC]=0.701，p=0.014）和较高的 MVD（AUC=0.821，p<0.001）与脑血管症状存在统计学显著相关性。通过术前 MRI 或 CTA 检测到的不稳定颈动脉斑块内 COX-2 的表达和巨噬细胞内 COX-2 染色强度显著更高（76.1% vs. 40.0%，p=0.038；76.2% vs. 30.0%，p=0.01）。
包括 MRI 或 CTA 在内的先进的非侵入性多模态诊断成像可可靠地区分不稳定和稳定的颈动脉斑块。在有症状斑块中，MMP-9 和 COX-2 在巨噬细胞中的高表达与增加脑血管并发症的风险相关。
本研究已在 ISRCTN 注册（ID ISRCTN46536832），ISRCTN 编号：https://www.isrctn.com/ISRCTN46536832。
