Temporal and quantitative analysis of expression of metalloproteinases (MMPs) and their endogenous inhibitors in atherosclerotic lesions.
Temporal and quantitative analysis of expression of metalloproteinases (MMPs) and their endogenous inhibitors in atherosclerotic lesions.
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DOI：
10.14670/hh-23.1503
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发表时间：
2008-12
影响因子：
2
通讯作者：
Ying Yu;T. Koike;S. Kitajima;Enqi Liu;M. Morimoto;M. Shiomi;K. Hatakeyama;Y. Asada;Ke-Yong Wang;Y. Sasaguri;Teruo Watanabe;Jianglin Fan
中科院分区：
文献类型：
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作者：
Ying Yu;T. Koike;S. Kitajima;Enqi Liu;M. Morimoto;M. Shiomi;K. Hatakeyama;Y. Asada;Ke-Yong Wang;Y. Sasaguri;Teruo Watanabe;Jianglin Fan
基质金属蛋白酶（MMP）在动脉粥样硬化、斑块破裂和动脉瘤等血管疾病的发病机制中发挥着重要作用。尽管已在动脉粥样硬化病变中证实了几种MMP，但其在病变发生和进展过程中的表达谱尚未完全确定。我们假设各种 MMP 及其内源性抑制剂的表达可能根据病变进展而受到差异性调节。因此，我们对兔和人动脉粥样硬化病变不同阶段表达的MMPs和金属蛋白酶组织抑制剂的mRNA和蛋白表达进行了时间和定量分析。我们发现正常动脉壁中MMP-1、MMP-12和MMP-13的表达几乎不存在，但随着病变进展而显着增加。此外，病灶中这些MMPs的表达与内膜巨噬细胞和单核细胞趋化蛋白1的表达密切相关，表明内膜巨噬细胞是这些MMPs的主要产生来源。与正常兔主动脉相比，MMP-3和MT1-MMP在早期病变和脂肪纹中也显着上调。我们的结果表明，源自内膜巨噬细胞的MMP-1、-12和-13可能在病变的发生和进展中发挥关键作用，因此是治疗斑块破裂和动脉瘤形成的潜在治疗靶点。
Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of vascular diseases, such as atherosclerosis, plaque rupture and aneurysms. Although several MMPs have been demonstrated in the lesions of atherosclerosis, their expression profiles during the initiation and progression of lesions have not been fully determined. We hypothesized that the expression of various MMPs, along with their endogenous inhibitors, may be differentially regulated dependent upon the lesion progression. Therefore, we made a temporal and quantitative analysis of the mRNA and protein expression of MMPs and tissue inhibitors of metalloproteinases expressed in the different stages of atherosclerotic lesions of rabbits and humans. We found that MMP-1, MMP-12 and MMP-13 expression was nearly absent in the normal arterial wall, but was remarkably increased with lesion progression. Furthermore, the expression of these MMPs in the lesions was closely associated with intimal macrophages and monocyte chemoattractant protein-1 expression, suggesting that the intimal macrophages are the major source of production of these MMPs. MMP-3 and MT1-MMP were also significantly upregulated in the early-stage lesions and fatty streaks compared to the normal aortas of rabbits. Our results indicate that MMP-1, -12, and -13 derived from intimal macrophages may play a pivotal role in both lesion initiation and progression, and therefore are potential therapeutic targets for the treatment of plaque rupture and aneurysm formation.