Metabolic Dysfunction in Heart Failure: Diagnostic, Prognostic, and Pathophysiologic Insights From Metabolomic Profiling.
Metabolic Dysfunction in Heart Failure: Diagnostic, Prognostic, and Pathophysiologic Insights From Metabolomic Profiling.
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DOI：
10.1007/s11897-016-0289-5
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发表时间：
2016-06
影响因子：
--
通讯作者：
Shah SH
中科院分区：
文献类型：
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作者：
Hunter WG;Kelly JP;McGarrah RW 3rd;Kraus WE;Shah SH
代谢障碍是心力衰竭（HF）病理生理学的一个内在组成部分。尽管最初被认为是心肌缺陷，但代谢功能障碍现在被认为是心肌与周围组织和器官之间复杂相互作用的系统过程。具体来说，心力衰竭相关的代谢功能障碍包括底物利用的改变、胰岛素抵抗、能量产生缺陷以及导致恶病质的合成代谢-分解代谢信号失衡。这些代谢异常中的每一种都与心力衰竭患者的显着发病率和死亡率相关。然而，它们的检测和治疗管理仍然具有挑战性。鉴于获取人类心脏组织用于研究目的的困难，外周血代谢组学分析是一种从典型生化途径中表征小分子代谢中间体的成熟方法，可能是剖析心力衰竭代谢损伤生物标志物和机制的有用技术。在这篇综述中，将讨论心力衰竭的代谢异常，特别强调代谢组学分析在检测、风险分层和确定这一异质人群代谢治疗新靶点中的应用。
Metabolic impairment is an intrinsic component of heart failure (HF) pathophysiology. Although initially conceived as a myocardial defect, metabolic dysfunction is now recognized as a systemic process with complex interplay between the myocardium and peripheral tissues and organs. Specifically, HF-associated metabolic dysfunction includes alterations in substrate utilization, insulin resistance, defects in energy production, and imbalanced anabolic-catabolic signaling leading to cachexia. Each of these metabolic abnormalities is associated with significant morbidity and mortality in patients with HF; however, their detection and therapeutic management remains challenging. Given the difficulty in obtaining human cardiac tissue for research purposes, peripheral blood metabolomic profiling, a well-established approach for characterizing small-molecule metabolite intermediates from canonical biochemical pathways, may be a useful technology for dissecting biomarkers and mechanisms of metabolic impairment in HF. In this review, metabolic abnormalities in HF will be discussed with particular emphasis on the application of metabolomic profiling to detecting, risk stratifying, and identifying novel targets for metabolic therapy in this heterogeneous population.