Collagenase matrix metalloproteinase-8 expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome
Collagenase matrix metalloproteinase-8 expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome
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DOI：
10.1093/eurheartj/ehq517
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发表时间：
2011-09-01
影响因子：
39.3
通讯作者：
Pasterkamp, Gerard
中科院分区：
文献类型：
--
作者：
Peeters, Wouter;Moll, Frans L.;Pasterkamp, Gerard
目的动脉粥样硬化斑块破裂和血栓形成是急性心血管事件的主要原因.局部斑块标记物可以促进易损斑块的检测，并有助于识别处于心血管事件风险中的患者。基质金属蛋白酶（MMP）在整个动脉系统的动脉壁中普遍存在，并且与局部斑块不稳定相关。我们假设，当地MMP斑块水平是预测动脉粥样硬化性心血管事件在其他vasculartargets.Methods和结果动脉粥样硬化斑块从543例接受颈动脉内膜切除术（CEA）。分析斑块中是否存在巨噬细胞、脂质核心、平滑肌细胞、胶原蛋白、钙化和斑块出血。在斑块内评估MMP-2、MMP-8和MMP-9水平。CEA后，所有患者均接受了3年的随访。主要结局定义为血管性死亡、非致死性血管事件和手术或经皮血管介入治疗的复合终点。与MMP-2斑块水平相反，斑块中MMP-8和MMP-9水平与基线时不稳定的颈动脉斑块组成和临床表现相关。斑块MMP-8水平升高（>4.58）与随访期间动脉粥样硬化性疾病继发表现发生风险增加相关[危害比= 1.76，95%CI（1.25-2.48）]而斑块MMP-2和MMP-9水平对全身性心血管事件无预测作用（P = 0.001）。增加的颈动脉MMP-8和MMP-9斑块水平与不稳定的斑块表型相关。颈动脉斑块中高胶原酶MMP-8水平与随访期间全身心血管结局的发生相关。
Aims Atherosclerotic plaque rupture and subsequent thrombus formation are the major cause of acute cardiovascular events. Local plaque markers may facilitate detection of the vulnerable plaque and help identify the patient at risk for cardiovascular events. Matrix metalloproteinases (MMPs) are prevalent in the arterial wall throughout the arterial system and are associated with local plaque destabilization. We hypothesized that local MMP plaque levels are predictive for atherosclerotic cardiovascular events in other vascular territories.Methods and results Atherosclerotic plaques were obtained from 543 patients undergoing carotid endarterectomy (CEA). Plaques were analysed for the presence of macrophages, lipid-core, smooth muscle cells, collagen, calcification, and presence of plaque haemorrhage. MMP-2, MMP-8, and MMP-9 levels were assessed within the plaque. Following CEA, all patients underwent follow-up during 3 years. The primary outcome was defined as the composite of vascular death, non-fatal vascular event, and surgical or percutaneous vascular intervention. In contrast with MMP-2 plaque levels, MMP-8 and MMP-9 levels in the plaque were associated with an unstable carotid plaque composition and clinical presentation at baseline. Increased plaque MMP-8 level (>4.58) was associated with an increased risk for the occurrence of secondary manifestations of atherosclerotic disease during follow-up [hazard ratio = 1.76, 95% CI (1.25-2.48)] (P = 0.001), whereas plaque MMP-2 and MMP-9 levels were not predictive for systemic cardiovascular events.Conclusion In contrast with MMP-2, increased carotid MMP-8 and MMP-9 plaque levels are associated with an unstable plaque phenotype. High collagenase MMP-8 levels in the carotid plaque are associated with the occurrence of systemic cardiovascular outcome during follow-up.