Matrix metalloproteinases and tissue inhibitors of metalloproteinases in hamster aortic atherosclerosis: correlation with in-situ zymography
Matrix metalloproteinases and tissue inhibitors of metalloproteinases in hamster aortic atherosclerosis: correlation with in-situ zymography
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DOI：
10.1016/s0021-9150(01)00590-1
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发表时间：
2002-02-01
期刊：
影响因子：
5.3
通讯作者：
Foxall, TL
中科院分区：
文献类型：
--
作者：
Faia, KL;Davis, WP;Foxall, TL
动脉粥样硬化需要细胞外基质（ECM）的改变，这一过程可能是由基质降解金属蛋白酶（MMPs）及其内源性组织抑制剂（TIMPs）介导的。本研究的目的是检测免疫组织化学表达模式；mmp -1, -2。-3和-9及其组织抑制剂TIMPs-1、-2、-3和-4在高胆固醇血症叙利亚金仓鼠动脉粥样硬化病变发展的三个主要阶段中的作用。在12周、24周和49周时对治疗仓鼠的主动脉粥样硬化病变（脂肪条纹、纤维脂肪和晚期）进行组织学表征。在有病变的治疗主动脉段和无病变的对照主动脉段中检测这些MMPs和TIMPs的免疫组织化学表达。MMP活性在对照主动脉和动脉粥样硬化病变中被原位酶谱法表征。mmp -2、-3、-9和TIMPs-1、-？MMP-1仅存在于动脉粥样硬化病变中，而MMP-1仅存在于动脉粥样硬化病变中。利用原位酶谱法，我们鉴定了脂肪条纹中酪蛋白和明胶的降解。纤维脂肪和晚期病变。在所有病变阶段，1.10-菲罗啉均能抑制底物降解。在对照主动脉中未观察到这些底物的降解。此外，1.10-菲罗啉抑制了底物降解。这些发现表明，在对照组中，净蛋白水解平衡向有利于MMP抑制的方向转移。另外。尽管MMPs和TIMPs在治疗节段的共定位。净蛋白水解平衡有利于催化MMPs。(C) 2002爱思唯尔科学爱尔兰有限公司版权所有。
Atherogenesis requires extracellular matrix (ECM) alterations, a process possibly mediated by matrix-degrading metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs). The objective of this study was to examine the immunohistochemical expression pattern; of MMPs-1, -2. -3 and -9 and their tissue inhibitors, TIMPs-1, -2, -3 and -4 during the three major stages of atherosclerotic lesion development in hypercholesterolemic Syrian Golden hamsters. Aortic atherosclerotic lesions (fatty streak, fibro-fatty and advanced) were histologically characterized in treated hamsters at 12, 24, and 49 weeks. The immunohistochemical expression of these MMPs and TIMPs were examined in treated aortic sections with lesions and control aortic sections without lesions. MMP activity in control aortas and atherosclerotic lesions was characterized by in-situ zymography. Positive immunoreactivity for MMPs-2, -3, -9 and TIMPs-1, -?,-3, and -4 was observed in both control and atherosclerotic aortic arch segments, while MMP-1 was only observed in atherosclerotic lesions. Using in-situ zymography, we identified casein and gelatin degradation in fatty streak. Fibro-fatty and advanced lesions. In all lesion stages, substrate degradation was inhibited with 1.10-phenanthroline. Degradation of these substrates was not observed in control aortas. In addition, substrate degradation was inhibited with 1.10-phenanthroline. These findings suggested that in control segments, the net proteolytic balance was shifted in favor of MMP inhibition. Alternatively. despite the colocalization of MMPs and TIMPs in the treated segments. net proteolytic balance favored the catalytic MMPs. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.