INTERSTITIAL COLLAGENASE (MMP-1) EXPRESSION IN HUMAN CAROTID ATHEROSCLEROSIS
INTERSTITIAL COLLAGENASE (MMP-1) EXPRESSION IN HUMAN CAROTID ATHEROSCLEROSIS
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DOI：
10.1161/01.cir.92.6.1393
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发表时间：
1995-09-15
期刊：
影响因子：
37.8
通讯作者：
CLOWES, AW
中科院分区：
文献类型：
--
作者：
NIKKARI, ST;OBRIEN, KD;CLOWES, AW
在人类动脉粥样硬化中，大多数临床事件发生在斑块完整性受损，导致出血和血栓形成。其中一种机制可能是斑块细胞释放基质降解蛋白酶，如间质胶原酶（基质金属蛋白酶-1，MMP-1），其降解两种主要的斑块结构蛋白，I型和III型胶原。本研究旨在确定MMP-1是否在人类动脉粥样硬化斑块中表达。方法和结果对20例人颈动脉内膜切除术标本进行原位杂交和免疫组化，以确定颈动脉粥样硬化病变中MMP-1的细胞来源和位置。6条非动脉粥样硬化的颈动脉也被研究。在靠近纤维帽和肩区脂质核边界的斑块巨噬细胞亚群中检测到强烈的MMP-1表达（mRNA和蛋白）。斑块平滑肌细胞和内皮细胞亚群也表达MMP-1。出血占据脂质核的百分比与脂质核周长MMP-1阳性百分比之间有很强的相关性（r= 0.823， P= 0.0001）。MMP-1未在非粥样硬化性颈动脉的任何细胞类型中检测到。结论：MMP-1在人颈动脉粥样硬化的多种细胞类型中均有表达，且该蛋白酶的表达与斑块不稳定的组织病理学证据存在相关性。由于MMP-1可以降解斑块的主要结构性胶原，巨噬细胞在斑块完整性关键区域表达蛋白酶可能导致斑块扩张、破裂和出血。
Background In human atherosclerosis, most clinical events occur when plaque integrity is compromised and hemorrhage and thrombosis result. One mechanism for this might be the release by plaque cells of matrix-degrading proteases, such as interstitial collagenase (matrix metalloproteinase-1, MMP-1), which degrades two major plaque structural proteins, types I and III collagen. This study was undertaken to determine whether MMP-1 is expressed in human atherosclerotic plaques.Methods and Results To determine the cellular source and location of MMP-1 in human carotid atherosclerotic lesions, in situ hybridization and immunohistochemistry were performed on 20 endarterectomy specimens. Six nonatherosclerotic carotid arteries also were studied. Intense MMP-1 expression (mRNA and protein) was detected in a subset of plaque macrophages located at the borders of the lipid cores adjacent to fibrous caps and shoulder regions. Subsets of plaque smooth muscle cells and endothelial cells also expressed MMP-1. There was a strong correlation between the percentage of the lipid core occupied by hemorrhage and the percentage of the lipid core perimeter positive for MMP-1 (r=.823, P=.0001). MMP-1 was not detected in any cell type in nonatherosclerotic carotid arteries.Conclusions This study demonstrates that MMP-1 is expressed by several cell types in human carotid atherosclerosis and that there is a correlation between the expression of the protease and histopathological evidence of plaque instability. Since MMP-1 may degrade the major structural collagens of the plaque, expression of the protease by macrophages in regions critical to plaque integrity could contribute to plaque expansion, rupture, and hemorrhage.