Unstable carotid plaques exhibit raised matrix metalloproteinase-8 activity
Unstable carotid plaques exhibit raised matrix metalloproteinase-8 activity
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DOI：
10.1161/01.cir.0000135588.65188.14
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发表时间：
2004-07-20
期刊：
影响因子：
37.8
通讯作者：
Loftus, IM
中科院分区：
文献类型：
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作者：
Molloy, KJ;Thompson, MM;Loftus, IM
背景-动脉粥样硬化斑块的纤维帽主要由 I 型和 III 型胶原蛋白组成。不稳定的颈动脉斑块的特点是其帽破裂，导致血栓栓塞和中风。引起斑块破坏的蛋白水解机制尚不清楚，但胶原蛋白溶解基质金属蛋白酶 (MMP) -1、-8 和 -13 可能与此有关。本研究的目的是量化颈动脉斑块中这些胶原酶的浓度，并确定它们与斑块不稳定标志物的关系。方法和结果-从 159 名接受颈动脉内膜切除术的患者中收集动脉粥样硬化斑块。确定颈动脉区域症状的存在和时间。通过经颅多普勒记录术前栓塞情况。评估每个斑块的不稳定组织学特征。使用 ELISA 定量斑块 MMP 浓度。在有症状患者的斑块（20.5 与 11.4 ng/g；P=0.0002）、栓塞阳性患者的斑块（22.7 与 13.5 ng/g；P=0.0037）以及显示破裂组织学证据的斑块（20.8 与 14.7 ng/g；P=0.0037）中观察到活性 MMP-8 浓度显着较高。 P=0.0036）。 MMP-1 和 MMP-13 水平没有差异。免疫组织化学、原位杂交和共定位研究证实斑块内存在 MMP-8 蛋白和 mRNA，并与巨噬细胞共定位。 结论——这些数据表明 MMP-8 的活性形式可能部分负责动脉粥样硬化斑块胶原帽的降解。这种酶代表了旨在稳定脆弱斑块的药物治疗的一个有吸引力的靶点。
Background-The fibrous cap of atherosclerotic plaques is composed predominantly of type I and III collagen. Unstable carotid plaques are characterized by rupture of their cap, leading to thromboembolism and stroke. The proteolytic mechanisms causing plaque disruption are undefined, but the collagenolytic matrix metalloproteinase (MMP) -1, -8, and -13 may be implicated. The aim of this study was to quantify the concentrations of these collagenases in carotid plaques and to determine their relationship to markers of plaque instability.Methods and Results-Atherosclerotic plaques were collected from 159 patients undergoing carotid endarterectomy. The presence and timing of carotid territory symptoms were ascertained. Preoperative embolization was recorded by transcranial Doppler. Each plaque was assessed for histological features of instability. Plaque MMP concentrations were quantified with ELISA. Significantly higher concentrations of active MMP-8 were observed in the plaques of symptomatic patients (20.5 versus 11.4 ng/g; P=0.0002), in plaques of emboli-positive patients (22.7 versus 13.5 ng/g; P=0.0037), and in those plaques showing histological evidence of rupture (20.8 versus 14.7 ng/g; P=0.0036). No differences were seen in the levels of MMP-1 and MMP-13. Immunohistochemistry, in situ hybridization, and colocalization studies confirmed the presence of MMP-8 protein and mRNA within the plaque, which colocalized with macrophages.Conclusions-These data suggest that the active form of MMP-8 may be partly responsible for degradation of the collagen cap of atherosclerotic plaques. This enzyme represents an attractive target for drug therapy aimed at stabilizing vulnerable plaques.