A 1H NMR based metabonomics approach to progression of coronary atherosclerosis in a rabbit model

A 1H NMR based metabonomics approach to progression of coronary atherosclerosis in a rabbit model
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基于 1H NMR 的代谢组学方法研究兔模型冠状动脉粥样硬化的进展

DOI:
10.1016/j.procbio.2011.08.016
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发表时间:
2011-12-01
影响因子:
4.4
通讯作者:
Zou, Zhong-Mei
Zou, Zhong-Mei
中科院分区:
生物学3区
文献类型:
--
作者:
Peng, Jing-Bo;Jia, Hong-Mei;Zou, Zhong-Mei

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氧化损伤和血管损伤与冠心病(CHD)的病理生理过程相对应,在氧化损伤和血管损伤之前和之后都伴随着微妙的代谢变化。为了研究冠状动脉粥样硬化的进展并识别潜在的生物标志物,使用质子核磁共振光谱(H-1 NMR)结合多变量数据分析研究了高胆固醇饮食家兔血浆中的代谢谱。动脉粥样硬化形成过程中代谢物的变化表现出从生理状态到病理生理状态的时间依赖性发展。基于NMR的血浆分析表明,低密度脂蛋白/极低密度脂蛋白(LDL/VLDL)、谷氨酰胺、磷酸胆碱、N-乙酰糖蛋白、甜菜碱、脯氨酸和酪氨酸是与主动脉粥样硬化病变最正相关的代谢物,而高密度脂蛋白(HDL)、不饱和脂质、柠檬酸盐、葡萄糖和肌酐是最负相关的代谢物。多种生化变化表明血脂异常,氧化应激,能量代谢的改变,和内皮功能障碍后胆固醇超载,并随后在兔早期冠状动脉粥样硬化。本研究表明,基于H-1 NMR的代谢组学可以为复杂的生理病理条件下的动态生化变化的调查提供有价值的信息。它也提供了一个有前途的非侵入性手段,发现生物标志物监测冠心病的发病和进展。(C)2011爱思唯尔有限公司保留所有权利。
Subtle metabolic variations precede and accompany oxidative and vascular damage, which correspond to the pathophysiological process of coronary heart disease (CHD). To investigate the progression of coronary atherosclerosis and identify potential biomarkers, the metabolic profiling in the plasma of rabbits fed a high-cholesterol diet were investigated using proton nuclear magnetic resonance spectroscopy (H-1 NMR) coupled with multivariate data analysis. Metabolite variations during atherogenesis showed a time-dependent development from physiological to pathophysiological status in rabbits. NMR-based plasma profiling demonstrated that low-density lipoprotein/very-low-density lipoprotein (LDL/VLDL), glutamine, phosphorylcholine, N-acetyl glycoproteins, betaine, proline, and tyrosine were the most positively corresponded metabolites of the aortic atherosclerotic lesions, whereas high-density lipoprotein (HDL), unsaturated lipids, citrate, glucose, and creatinine were the most negatively correlated metabolites. Multiple biochemical changes indicated dyslipidemia, oxidative stress, alteration of energy metabolism, and endothelial dysfunction after cholesterol overloading, and subsequently to early coronary atherosclerosis in rabbits. This study indicated that H-1 NMR based metabonomics can provide valuable information for the investigation of the dynamic biochemical variations underlying complex physiopathological conditions. It also offers a promising non-invasive means to the discovery of biomarkers for monitoring the onset and progression of CHD. (C) 2011 Elsevier Ltd. All rights reserved.