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主动脉夹层发病后,肉芽组织反应中基质金属蛋白酶-2和膜型1基质金属蛋白酶的上调与I型前胶原的上调相关。

Up-regulation of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase were coupled with that of type I procollagen in granulation tissue response after the onset of aortic dissection.

作者信息

Akiyama Masatoshi, Ohtani Haruo, Sato Eiichi, Nagura Hiroshi, Tabayashi Koichi

机构信息

Department of Cardiovascular Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Sendai 980-8574, Japan.

出版信息

Virchows Arch. 2006 Jun;448(6):811-21. doi: 10.1007/s00428-006-0194-5. Epub 2006 Apr 12.

Abstract

The pathophysiological significance of matrix metalloproteinases (MMPs) in aortic dissection remains poorly understood. The purpose of the present study is to clarify the significance of MMPs in aortic dissection. The activities and distributions of MMP-2, membrane-type 1-MMP (MT1-MMP), and MMP-9 were evaluated by gelatin zymography, immunohistochemistry, and in situ hybridization in 29 patients and seven autopsy cases. To assess if these MMPs are related to a tissue remodeling process, we compared the expression of these MMPs with that of type I procollagen and platelet-derived growth factor receptor beta chain (PDGF Rbeta). Patients were divided into three groups based on histological findings: acute, intermediate, and healed groups. The most remarkable changes were observed in the intermediate group, in which MMP-2 activity peaked and tissue expression of mRNAs for MMP-2 and MT1-MMP were observed in spindle-shaped cells in the neointima, organizing thrombus, and the adventitia. These expression patterns were essentially coupled with those of type I procollagen mRNA and PDGF-Rbeta protein. The association of MMP-2, MT1-MMP, type I procollagen, and PDGF-Rbeta suggests that MMP-2 and MT1-MMP could be involved not only in the degradation of aortic tissue but also in tissue remodeling, which may be associated with the healing process.

摘要

基质金属蛋白酶(MMPs)在主动脉夹层中的病理生理意义仍未完全明确。本研究旨在阐明MMPs在主动脉夹层中的意义。采用明胶酶谱法、免疫组织化学和原位杂交技术,对29例患者及7例尸检病例的MMP-2、膜型1-MMP(MT1-MMP)和MMP-9的活性及分布进行了评估。为了评估这些MMPs是否与组织重塑过程相关,我们将这些MMPs的表达与I型前胶原和血小板衍生生长因子受体β链(PDGF Rβ)的表达进行了比较。根据组织学结果将患者分为三组:急性组、中间组和愈合组。在中间组观察到最显著的变化,其中MMP-2活性达到峰值,并且在内膜下的梭形细胞、机化血栓和外膜中观察到MMP-2和MT1-MMP的mRNA组织表达。这些表达模式基本上与I型前胶原mRNA和PDGF-Rβ蛋白的表达模式相关。MMP-2、MT1-MMP、I型前胶原和PDGF-Rβ之间的关联表明,MMP-2和MT1-MMP不仅可能参与主动脉组织的降解,还可能参与组织重塑,这可能与愈合过程有关。

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