Combined metabolomic and proteomic analysis of human atrial fibrillation
Combined metabolomic and proteomic analysis of human atrial fibrillation
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DOI：
10.1016/j.jacc.2007.09.055
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发表时间：
2008-02-05
影响因子：
24
通讯作者：
Camm, A. John
中科院分区：
文献类型：
--
作者：
Mayr, Manuel;Yusuf, Shamil;Camm, A. John
目的我们试图解释持续性心房颤动（AF）期间增加的能量需求的代谢过程，并确定代谢紊乱是否可能诱发这种心律失常。心脏代谢对这种弹性心律失常的持续/开始的影响尚未被详细研究。方法来自窦性心律（SR）的匹配队列的人心房附件组织，结果高分辨率质子核磁共振（NMR）波谱分析显示，持续性房颤患者的心脏组织中β-羟基丁酸（酮体代谢的主要底物）含量增加，沿着生酮氨基酸和甘氨酸含量增加。这些代谢组学的研究结果证实了蛋白质组学实验表明差异表达的3-酮酸转移酶，酮解能量生产的关键酶。值得注意的是，与SR队列相比，易患术后AF的组显示出能量代谢的不一致调节。结合主成分和线性判别分析的代谢谱质子NMR光谱正确分类超过80%的患者在AF的风险，在冠状动脉旁路移植术的时间。结论本研究的特点是代谢适应持续性AF，解开酮体的潜在作用，并表明，不一致的代谢改变是明显的个人容易术后AF。
Objectives We sought to decipher metabolic processes servicing the increased energy demand during persistent atrial fibrillation (AF) and to ascertain whether metabolic derangements might instigate this arrhythmia.Background Whereas electrical, structural, and contractile remodeling processes are well-recognized contributors to the self-perpetuating nature of AF, the impact of cardiac metabolism upon the persistence/initiation of this resilient arrhythmia has not been explored in detail.Methods Human atrial appendage tissues from matched cohorts in sinus rhythm (SR), from those who developed AF post-operatively, and from patients in persistent AF undergoing cardiac surgery were analyzed using a combined metabolomic and proteomic approach.Results High-resolution proton nuclear magnetic resonance (NMR) spectroscopy of cardiac tissue from patients in persistent AF revealed a rise in beta-hydroxybutyrate, the major substrate in ketone body metabolism, along with an increase in ketogenic amino acids and glycine. These metabolomic findings were substantiated by proteomic experiments demonstrating differential expression of 3-oxoacid transferase, the key enzyme for ketolytic energy production. Notably, compared with the SR cohort, the group susceptible to post-operative AF showed a discordant regulation of energy metabolites. Combined principal component and linear discriminant analyses of metabolic profiles from proton NMR spectroscopy correctly classified more than 80% of patients at risk of AF at the time of coronary artery bypass grafting.Conclusions The present study characterized the metabolic adaptation to persistent AF, unraveling a potential role for ketone bodies, and demonstrated that discordant metabolic alterations are evident in individuals susceptible to postoperative AF.