Proteomic diversity of high-density lipoprotein explains its association with clinical outcome in patients with heart failure

Proteomic diversity of high-density lipoprotein explains its association with clinical outcome in patients with heart failure
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DOI:
10.1002/ejhf.1101
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发表时间:
2018-02-01
影响因子:
18.2
通讯作者:
Ng, Leong L.
Ng, Leong L.
中科院分区:
医学1区
文献类型:
--
作者:
Emmens, Johanna Elisabeth;Jones, Donald J. L.;Ng, Leong L.

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此前,低高密度脂蛋白(HDL)胆固醇被发现是心衰患者死亡率和/或心衰住院的最强预测因子之一。因此,我们对多功能HDL蛋白质组进行了深入的研究,以揭示解释HDL与临床结果之间关系的潜在病理生理机制。方法和结果我们从BIOSTAT-CHE中选择了90例心血管死亡/存活比例为1:1的HF患者,采用了一种新的优化的脂蛋白选择性富集方案来制备血浆。利用无标记方法,利用高分辨率纳米级液相色谱-质谱技术分析样品的富集脂蛋白含量。在高密度脂蛋白蛋白质组中,死亡和幸存者之间有49种蛋白质显著不同。一个由12种蛋白质组成的优化模型预测死亡的准确率为76% (Nagelkerke R-2 =0.37, P
Aims Previously, low high-density lipoprotein (HDL) cholesterol was found to be one of the strongest predictors of mortality and/or heart failure (HF) hospitalisation in patients with HF. We therefore performed in-depth investigation of the multifunctional HDL proteome to reveal underlying pathophysiological mechanisms explaining the association between HDL and clinical outcome.Methods and results We selected a cohort of 90 HF patients with 1:1 cardiovascular death/survivor ratio from BIOSTAT-CHE A novel optimised protocol for selective enrichment of lipoproteins was used to prepare plasma. Enriched lipoprotein content of samples was analysed using high resolution nanoscale liquid chromatography-mass spectrometry-based proteomics, utilising a label free approach. Within the HDL proteome, 49 proteins significantly differed between deaths and survivors. An optimised model of 12 proteins predicted death with 76% accuracy (Nagelkerke R-2 =0.37, P