Matrix metalloproteinase 7 is associated with symptomatic lesions and adverse events in patients with carotid atherosclerosis.
Matrix metalloproteinase 7 is associated with symptomatic lesions and adverse events in patients with carotid atherosclerosis.
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DOI：
10.1371/journal.pone.0084935
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Halvorsen B
中科院分区：
文献类型：
--
作者：
Abbas A;Aukrust P;Russell D;Krohg-Sørensen K;Almås T;Bundgaard D;Bjerkeli V;Sagen EL;Michelsen AE;Dahl TB;Holm S;Ueland T;Skjelland M;Halvorsen B
动脉粥样硬化是脑血管疾病的主要原因。基质金属蛋白酶 (MMP) 在动脉粥样硬化病变内的基质降解中发挥重要作用，导致斑块不稳定和缺血性中风。我们假设 MMP-7 可能参与这个过程。对 182 名连续中度（50-69%）或重度（≥70%）颈内动脉狭窄患者以及 23 名健康对照者的血浆 MMP-7 水平进行了测量。测量具有不同症状的动脉粥样硬化颈动脉斑块中MMP-7的mRNA水平，并基于其在巨噬细胞中的定位，检查原代单核细胞中MMP-7的体外调节。我们的主要发现是 (i) 与健康对照相比，颈动脉粥样硬化患者的血浆 MMP-7 水平显着升高，尤其是最近出现症状的患者（即过去 2 个月内）的水平尤其高。 (ii) 在颈动脉斑块中发现了类似的模式，其 MMP-7 mRNA 水平显着高于非动脉粥样硬化血管。最近出现症状的患者的 MMP-7 蛋白水平特别高。 (iii)免疫组织化学显示MMP-7定位于巨噬细胞，原代单核细胞的体外研究表明炎症细胞因子肿瘤坏死因子-α与缺氧和氧化LDL结合显着增加MMP-7表达。 (iv) 在颈动脉粥样硬化患者的随访过程中，高血浆 MMP-7 水平与总死亡率独立相关。我们的研究结果表明，MMP-7 可能导致颈动脉粥样硬化斑块不稳定，可能涉及巨噬细胞相关机制。
Atherosclerosis is a major cause of cerebrovascular disease. Matrix metalloproteinases (MMPs) play an important role in matrix degradation within the atherosclerotic lesion leading to plaque destabilization and ischemic stroke. We hypothesized that MMP-7 could be involved in this process. Plasma levels of MMP-7 were measured in 182 consecutive patients with moderate (50–69%) or severe (≥70%) internal carotid artery stenosis, and in 23 healthy controls. The mRNA levels of MMP-7 were measured in atherosclerotic carotid plaques with different symptomatology, and based on its localization to macrophages, the in vitro regulation of MMP-7 in primary monocytes was examined. Our major findings were (i) Patients with carotid atherosclerosis had markedly increased plasma levels of MMP-7 compared to healthy controls, with particularly high levels in patients with recent symptoms (i.e., within the last 2 months). (ii) A similar pattern was found within carotid plaques with markedly higher mRNA levels of MMP-7 than in non-atherosclerotic vessels. Particularly high protein levels of MMP-7 levels were found in those with the most recent symptoms. (iii) Immunhistochemistry showed that MMP-7 was localized to macrophages, and in vitro studies in primary monocytes showed that the inflammatory cytokine tumor necrosis factor-α in combination with hypoxia and oxidized LDL markedly increased MMP-7 expression. (iv) During the follow-up of patients with carotid atherosclerosis, high plasma levels of MMP-7 were independently associated with total mortality. Our findings suggest that MMP-7 could contribute to plaque instability in carotid atherosclerosis, potentially involving macrophage-related mechanisms.
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影响因子：
5.3
作者：
Furman, C;Copin, C;Rouis, M
通讯作者：
Rouis, M
影响因子：
4.1
作者：
Halvorsen, B;Aas, UK;Kolset, SO
通讯作者：
Kolset, SO
DOI：
10.1016/j.ejvs.2011.05.023
发表时间：
2011-12-01
影响因子：
5.7
作者：
Razuvaev, A.;Ekstrand, J.;Hedin, U.
通讯作者：
Hedin, U.
影响因子：
3.8
作者：
Stylianou, E;Aukrust, P;Froland, SS
通讯作者：
Froland, SS
影响因子：
2.9
作者：
Pelisek, Jaroslav;Rudelius, Martina;Eckstein, Hans-Henning
通讯作者：
Eckstein, Hans-Henning