Quantitative Proteomics of Changes in Energy Metabolism-Related Proteins in Atrial Tissue From Valvular Disease Patients With Permanent Atrial Fibrillation

Quantitative Proteomics of Changes in Energy Metabolism-Related Proteins in Atrial Tissue From Valvular Disease Patients With Permanent Atrial Fibrillation
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DOI:
10.1253/circj.cj-13-1365
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发表时间:
2014-04-01
影响因子:
3.3
通讯作者:
Liu, Qiming
Liu, Qiming
中科院分区:
医学3区
文献类型:
--
作者:
Tu, Tao;Zhou, Shenghua;Liu, Qiming

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背景:既往研究已证实心房颤动(AF)期间心脏能量代谢的改变,表明这两个过程之间存在密切关联。本研究的目的是通过分析心房颤动患者左心房附件(LAA)能量代谢相关蛋白的表达来确定其潜在的机制。方法和结果:采用相对和绝对定量等压标签-耦合二维液相色谱-串联质谱(itraq -耦合二维LC-MS/MS)分析瓣膜性疾病合并窦性心律(SR)患者左心房附件(LAA)能量代谢相关蛋白的表达;n=6)和AF (n=8)。利用Protein Pilot 4.0,共鉴定了122种能量代谢相关蛋白,其中碳水化合物代谢相关蛋白39种,脂质代谢相关蛋白22种,生物氧化相关蛋白49种,其他蛋白12种。其中大部分是参与能量代谢的关键酶。此外,AF和SR患者LAA中表达差异的、与能量代谢相关的大部分蛋白均下调。这些结果在western blot上得到进一步验证。结论:永久性房颤时,瓣膜性疾病患者心房心肌能量产生受损,这种能量产生受损可能与房颤形成基质有关。
Background: The modification of cardiac energy metabolism during atrial fibrillation (AF) has been demonstrated in previous studies, indicating a close association between these 2 processes. The aim of the present study was to identify the underlying mechanisms via profiling of the expression of energy metabolism-related proteins in the left atrial appendage (LAA) of patients with AF.Methods and Results: Isobaric tag for relative and absolute quantification-coupled 2-D liquid chromatography-tandem mass spectrometry (iTRAQ-coupled 2-D LC-MS/MS) was used to profile the expression of energy metabolism-related proteins in the LAA from valvular disease patients with sinus rhythm (SR; n=6) and AF (n=8). Using Protein Pilot 4.0, 122 energy metabolism-related proteins, consisting of 39 carbohydrate metabolism-related proteins, 22 proteins involved in lipid metabolism, 49 biological oxidation-related proteins and 12 other kinds of proteins, were identified. Most of them were key enzymes involved in energy metabolism. Moreover, most of the proteins that were expressed differently in the LAA between the AF and SR patients, and which were related to energy metabolism, were down-regulated. These results were further validated on western blot.Conclusions: Atrial myocardium energy production in valvular disease patients is impaired during permanent AF, and this impairment in energy production may be involved in the matrix of AF formation.