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血清脂质组学与心脏磁共振成像:扩张型心肌病风险患者的特征分析。

Serum lipidomics meets cardiac magnetic resonance imaging: profiling of subjects at risk of dilated cardiomyopathy.

机构信息

VTT Technical Research Centre of Finland, Espoo, Finland.

出版信息

PLoS One. 2011 Jan 20;6(1):e15744. doi: 10.1371/journal.pone.0015744.

Abstract

Dilated cardiomyopathy (DCM), characterized by left ventricular dilatation and systolic dysfunction, constitutes a significant cause for heart failure, sudden cardiac death or need for heart transplantation. Lamin A/C gene (LMNA) on chromosome 1p12 is the most significant disease gene causing DCM and has been reported to cause 7-9% of DCM leading to cardiac transplantation. We have previously performed cardiac magnetic resonance imaging (MRI) to LMNA carriers to describe the early phenotype. Clinically, early recognition of subjects at risk of developing DCM would be important but is often difficult. Thus we have earlier used the MRI findings of these LMNA carriers for creating a model by which LMNA carriers could be identified from the controls at an asymptomatic stage. Some LMNA mutations may cause lipodystrophy. To characterize possible effects of LMNA mutations on lipid profile, we set out to apply global serum lipidomics using Ultra Performance Liquid Chromatography coupled to mass spectrometry in the same LMNA carriers, DCM patients without LMNA mutation and controls. All DCM patients, with or without LMNA mutation, differed from controls in regard to distinct serum lipidomic profile dominated by diminished odd-chain triglycerides and lipid ratios related to desaturation. Furthermore, we introduce a novel approach to identify associations between the molecular lipids from serum and the MR images from the LMNA carriers. The association analysis using dependency network and regression approaches also helped us to obtain novel insights into how the affected lipids might relate to cardiac shape and volume changes. Our study provides a framework for linking serum derived molecular markers not only with clinical endpoints, but also with the more subtle intermediate phenotypes, as derived from medical imaging, of potential pathophysiological relevance.

摘要

扩张型心肌病(DCM)以左心室扩张和收缩功能障碍为特征,是心力衰竭、心源性猝死或需要心脏移植的重要原因。染色体 1p12 上的核纤层蛋白 A/C 基因(LMNA)是导致 DCM 的最重要疾病基因,据报道,它导致 7-9%的 DCM 需要进行心脏移植。我们之前已经对 LMNA 携带者进行了心脏磁共振成像(MRI)检查,以描述其早期表型。临床上,早期识别有发生 DCM 风险的患者非常重要,但往往很难做到。因此,我们之前使用这些 LMNA 携带者的 MRI 结果创建了一个模型,通过该模型可以在无症状阶段从对照组中识别出 LMNA 携带者。一些 LMNA 突变可能导致脂肪营养不良。为了描述 LMNA 突变对脂质谱的可能影响,我们着手在相同的 LMNA 携带者、无 LMNA 突变的 DCM 患者和对照组中使用超高效液相色谱-质谱联用技术进行全局血清脂质组学分析。所有 DCM 患者,无论是否存在 LMNA 突变,与对照组相比,其血清脂质谱均存在明显差异,特征为奇数链甘油三酯减少和与去饱和相关的脂质比值。此外,我们提出了一种新方法来识别来自血清的分子脂质与来自 LMNA 携带者的 MRI 图像之间的关联。使用依赖网络和回归方法的关联分析也帮助我们获得了关于受影响脂质如何与心脏形状和体积变化相关的新见解。我们的研究为将血清中衍生的分子标志物不仅与临床终点,而且与更微妙的中间表型(源自医学影像学)联系起来提供了一个框架,这些中间表型具有潜在的病理生理学相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9c/3024392/6c6271b61987/pone.0015744.g001.jpg

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