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人类腹主动脉瘤与糖胺聚糖水平的成分和特定结构改变密切相关。

Human abdominal aortic aneurysm is closely associated with compositional and specific structural modifications at the glycosaminoglycan level.

作者信息

Theocharis A D, Tsolakis I, Tsegenidis T, Karamanos N K

机构信息

Department of Chemistry, University of Patras, Greece.

出版信息

Atherosclerosis. 1999 Aug;145(2):359-68. doi: 10.1016/s0021-9150(99)00117-3.

DOI:10.1016/s0021-9150(99)00117-3
PMID:10488964
Abstract

Human abdominal aortic aneurysm (AAA) is a commonly occuring disease of blood vessels and is related to alterations in extracellular matrix molecules. In this study we report on the type and fine structural characterization of glycosaminoglycans (GAGs) present in AAA as compared with those present in normal abdominal aorta. Hyaluronan (HA), the galactosaminoglycans-chondroitin sulfate (CS) and dermatan sulfate (DS) with average molecular size (Mr) of 35-kDa-as well as heparan sulfate (HS) with Mr of 40-kDa were identified in both tissues. No significant intrabatch differences in total GAG content were identified in normal and aneurysmal aortas. Comparing, however, tissue composition and structure of GAGs between AAAs and normal aortas, significant differences (P < or = 0.001) were found. The overall GAG content in AAAs was approx. 60% lower than the normal ones. A 90% decrease in HS content, and 65 and 73% in CS and HA, respectively, were also recorded. In contrast, only a slight decrease in the amount of DS was noted (8%). Structural alterations in disaccharide composition of GAGs correspond mainly to significant decreases (P < or = 0.001) of HS-derived N-sulfated disaccharides, CS-derived 6-sulfated disaccharide and DS-derived disulfated disaccharides. These results demonstrate that the development of AAA is related to dramatic quantitative and structural modifications at the GAG level and this may well be attributed to the destruction of arterial wall architecture and further significant functional inadequacies of the tissue.

摘要

人类腹主动脉瘤(AAA)是一种常见的血管疾病,与细胞外基质分子的改变有关。在本研究中,我们报告了与正常腹主动脉相比,AAA中存在的糖胺聚糖(GAG)的类型和精细结构特征。在两种组织中均鉴定出透明质酸(HA)、平均分子量(Mr)为35 kDa的半乳糖胺聚糖 - 硫酸软骨素(CS)和硫酸皮肤素(DS)以及Mr为40 kDa的硫酸乙酰肝素(HS)。在正常和动脉瘤主动脉中未发现总GAG含量的显著批次内差异。然而,比较AAA和正常主动脉之间GAG的组织组成和结构,发现了显著差异(P≤0.001)。AAA中的总GAG含量比正常主动脉低约60%。还记录到HS含量降低了90%,CS和HA含量分别降低了65%和73%。相比之下,仅观察到DS含量略有下降(8%)。GAG二糖组成的结构改变主要对应于HS衍生的N - 硫酸化二糖、CS衍生的6 - 硫酸化二糖和DS衍生的二硫酸化二糖的显著减少(P≤0.001)。这些结果表明,AAA的发展与GAG水平的显著定量和结构改变有关,这很可能归因于动脉壁结构的破坏以及组织进一步的显著功能不足。

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