Matrix vesicles in the fibrous cap of atherosclerotic plaque: possible contribution to plaque rupture.
Matrix vesicles in the fibrous cap of atherosclerotic plaque: possible contribution to plaque rupture.
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DOI：
10.1111/j.1582-4934.2008.00230.x
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发表时间：
2008-10
影响因子：
5.3
通讯作者：
Grabs AJ
中科院分区：
文献类型：
--
作者：
Bobryshev YV;Killingsworth MC;Lord RS;Grabs AJ
斑块破裂是最常见的斑块并发症类型，并导致急性缺血性事件，如心肌梗死和中风。钙化被认为是斑块不稳定的一个可能的指标。虽然基质囊泡在动脉钙化的初始阶段的作用已被认可，但尚未进行研究以检查基质囊泡在斑块不稳定中的可能作用。本研究选择的组织标本代表接受颈动脉内膜切除术患者的颈动脉标本。切割组织标本的连续冷冻横截面并固定在载玻片上。在每个晚期动脉粥样硬化病变的纤维帽（FCT）的厚度，包含一个发育良好的脂质/坏死的核心，在其最靠近的网站在连续切片组测量。根据已建立的标准，动脉粥样硬化斑块标本在组织学上分为两组：具有薄纤维帽（FCT <100 μm）的易损斑块和纤维帽厚于100 μm的假定稳定斑块。收集了24个颈动脉斑块（12个易损斑块和12个可能稳定的斑块），用于纤维帽中基质囊泡的分析。为了从每个斑块提供足够数量的代表性区域，进行激光捕获显微切割（LCM）。对易损斑块和稳定斑块切片中基质囊泡的定量显示，易损斑块纤维帽中基质囊泡的数量显著高于稳定斑块（每1.92 μm2标准面积8.908±0.544 vs 6.208±0.467基质囊泡; P= 0.0002）。电子显微镜结合X射线元素微区分析显示，动脉粥样硬化斑块中的一些基质囊泡正在发生钙化，其特征在于高含量的钙和磷。易损斑块纤维帽中钙化基质囊泡/微钙化百分比显著高于稳定斑块（6.705± 0.436vs5.322 ± 0.94，P= 0.0474）。这一发现强化了这样一种观点，即动脉粥样硬化斑块变薄的纤维帽中细胞外基质的质地发生了改变，这可能有助于斑块的不稳定。
Plaque rupture is the most common type of plaque complication and leads to acute ischaemic events such as myocardial infarction and stroke. Calcification has been suggested as a possible indicator of plaque instability. Although the role of matrix vesicles in the initial stages of arterial calcification has been recognized, no studies have yet been carried out to examine a possible role of matrix vesicles in plaque destabilization. Tissue specimens selected for the present study represented carotid specimens obtained from patients undergoing carotid endarterectomy. Serial frozen cross-sections of the tissue specimens were cut and mounted on glass slides. The thickness of the fibrous cap (FCT) in each advanced atherosclerotic lesion, containing a well developed lipid/necrotic core, was measured at its narrowest sites in sets of serial sections. According to established criteria, atherosclerotic plaque specimens were histologically subdivided into two groups: vulnerable plaques with thin fibrous caps (FCT <100 μm) and presumably stable plaques, in which fibrous caps were thicker than 100 μm. Twenty-four carotid plaques (12 vulnerable and 12 presumably stable plaques) were collected for the present analysis of matrix vesicles in fibrous caps. In order to provide a sufficient number of representative areas from each plaque, laser capture microdissection (LCM) was carried out. The quantification of matrix vesicles in ultrathin sections of vulnerable and stable plaques revealed that the numbers of matrix vesicles were significantly higher in fibrous caps of vulnerable plaques than those in stable plaques (8.908±0.544 versus 6.208±0.467 matrix vesicles per 1.92 μm2 standard area; P= 0.0002). Electron microscopy combined with X-ray elemental microanalysis showed that some matrix vesicles in atherosclerotic plaques were undergoing calcification and were characterized by a high content of calcium and phosphorus. The percentage of calcified matrix vesicles/microcalcifications was significantly higher in fibrous caps in vulnerable plaques compared with that in stable plaques (6.705±0.436 versus 5.322±0A94; P= 0.0474). The findings reinforce a view that the texture of the extracellular matrix in the thinning fibrous cap of atherosclerotic plaque is altered and this might contribute to plaque destabilization.