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人血浆硫酸软骨素异构体与颈动脉粥样硬化斑块之间的关联

Association between Human Plasma Chondroitin Sulfate Isomers and Carotid Atherosclerotic Plaques.

作者信息

Zinellu Elisabetta, Lepedda Antonio Junior, Cigliano Antonio, Pisanu Salvatore, Zinellu Angelo, Carru Ciriaco, Bacciu Pietro Paolo, Piredda Franco, Guarino Anna, Spirito Rita, Formato Marilena

机构信息

Dipartimento di Scienze Fisiologiche, Biochimiche e Cellulari, Università delgi Studi di Sassari, 07100 Sassari, Italy.

出版信息

Biochem Res Int. 2012;2012:281284. doi: 10.1155/2012/281284. Epub 2011 Dec 15.

Abstract

Several studies have evidenced variations in plasma glycosaminoglycans content in physiological and pathological conditions. In normal human plasma GAGs are present mainly as undersulfated chondroitin sulfate (CS). The aim of the present study was to evaluate possible correlations between plasma CS level/structure and the presence/typology of carotid atherosclerotic lesion. Plasma CS was purified from 46 control subjects and 47 patients undergoing carotid endarterectomy showing either a soft or a hard plaque. The concentration and structural characteristics of plasma CS were assessed by capillary electrophoresis of constituent unsaturated fluorophore-labeled disaccharides. Results showed that the concentration of total CS isomers was increased by 21.4% (P < 0.01) in plasma of patients, due to a significant increase of undersulfated CS. Consequently, in patients the plasma CS charge density was significantly reduced with respect to that of controls. After sorting for plaque typology, we found that patients with soft plaques and those with hard ones differently contribute to the observed changes. In plasma from patients with soft plaques, the increase in CS content was not associated with modifications of its sulfation pattern. On the contrary, the presence of hard plaques was associated with CS sulfation pattern modifications in presence of quite normal total CS isomers levels. These results suggest that the plasma CS content and structure could be related to the presence and the typology of atherosclerotic plaque and could provide a useful diagnostic tool, as well as information on the molecular mechanisms responsible for plaque instability.

摘要

多项研究已证明,在生理和病理条件下血浆糖胺聚糖含量存在差异。在正常人体血浆中,糖胺聚糖主要以低硫酸化硫酸软骨素(CS)的形式存在。本研究的目的是评估血浆CS水平/结构与颈动脉粥样硬化病变的存在/类型之间可能存在的相关性。从46名对照受试者和47名接受颈动脉内膜切除术且有软斑块或硬斑块的患者中纯化血浆CS。通过对组成的不饱和荧光团标记二糖进行毛细管电泳来评估血浆CS的浓度和结构特征。结果显示,患者血浆中总CS异构体的浓度增加了21.4%(P < 0.01),这是由于低硫酸化CS显著增加所致。因此,与对照组相比,患者血浆CS的电荷密度显著降低。在对斑块类型进行分类后,我们发现软斑块患者和硬斑块患者对观察到的变化的贡献不同。在软斑块患者的血浆中,CS含量的增加与其硫酸化模式的改变无关。相反,硬斑块的存在与总CS异构体水平相当正常情况下的CS硫酸化模式改变有关。这些结果表明,血浆CS的含量和结构可能与动脉粥样硬化斑块的存在和类型有关,并可能提供一种有用的诊断工具,以及有关斑块不稳定分子机制的信息。

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