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基质金属蛋白酶及其内源性抑制剂在腹主动脉瘤和主髂动脉闭塞性疾病(勒里什综合征)中的表达

Expression of Matrix Metalloproteinases and Endogenous Inhibitors in Abdominal Aortic Aneurysm and Aortoiliac Occlusive Disease (Syndrome Leriche).

作者信息

Vasic N, Glumac S, Pejic S, Amidzic L J, Tadic Latinovic L J, Dozic B, Hinic S, Maksimovic Z

机构信息

Department of Vascular Surgery; University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina.

Institute of Pathology, School of Medicine, University Clinical Hospital Centre "Bezanijska kosa"; University of Belgrade, Belgrade, Serbia.

出版信息

Folia Biol (Praha). 2017;63(5-6):209-216. doi: 10.14712/fb2017063050209.

DOI:10.14712/fb2017063050209
PMID:29687775
Abstract

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a complex role in the pathogenesis of atherosclerosis. We compared (1) the histopathological findings in patients with abdominal aortic aneurysms (AAA) and aortoiliac occlusive disease (AOD); (2) the expression of MMP-2/MMP-9 and TIMP-1/TIMP-2 in aortic layers, inflammatory cells and smooth muscle cells (SMCs), aiming to identify the common underlying pathogenic mechanisms of the disease development. Samples were obtained from 30 patients with AAA and 30 with AOD. Aortic histology and immunohistochemistry were performed to evaluate inflammatory changes and MMP and TIMP expression. Thrombosis and ulceration were more frequent in AOD than in AAA. The MMP-9 expression was elevated in all aortic layers of AAA patients and in media/adventitia of AOD patients, mainly followed by lower expression of its inhibitor TIMP-1. Higher MMP-9 expression was also found in SMCs and macrophages of both AAA and AOD specimens, while higher TIMP-1/TIMP-2 were predominantly observed in the lymphocytes and macrophages of the aneurysm. These results showed that both conditions exhibited increased MMP-9 expression; however, the MMP expression pattern differed to some degree between the aneurysms and occlusive disease. The variations in molecular mechanisms underlying dilatative/stenosing disease warrant further investigation.

摘要

基质金属蛋白酶(MMPs)及其组织抑制剂(TIMPs)在动脉粥样硬化的发病机制中发挥着复杂的作用。我们比较了:(1)腹主动脉瘤(AAA)患者和主-髂动脉闭塞性疾病(AOD)患者的组织病理学发现;(2)MMP-2/MMP-9和TIMP-1/TIMP-2在主动脉各层、炎症细胞和平滑肌细胞(SMC)中的表达,旨在确定疾病发展的共同潜在致病机制。从30例AAA患者和30例AOD患者中获取样本。进行主动脉组织学和免疫组织化学检查以评估炎症变化以及MMP和TIMP的表达。AOD中血栓形成和溃疡比AAA更常见。AAA患者的所有主动脉层以及AOD患者的中膜/外膜中MMP-9表达升高,主要随后是其抑制剂TIMP-1的较低表达。在AAA和AOD标本的SMC和巨噬细胞中也发现较高的MMP-9表达,而在动脉瘤的淋巴细胞和巨噬细胞中主要观察到较高的TIMP-1/TIMP-2。这些结果表明,两种情况均表现出MMP-9表达增加;然而,动脉瘤和闭塞性疾病之间的MMP表达模式在一定程度上有所不同。扩张性/狭窄性疾病潜在分子机制的差异值得进一步研究。

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