Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury
Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury
复制标题
DOI：
10.1172/jci35111
复制
发表时间：
2008-10-01
影响因子：
15.9
通讯作者：
Gerszten, Robert E.
中科院分区：
文献类型：
--
作者：
Lewis, Gregory D.;Wei, Ru;Gerszten, Robert E.
新兴的代谢组学工具为建立心肌损伤的代谢特征创造了机会。我们将基于质谱的代谢物分析平台应用于36例接受酒精室间隔消融治疗的肥厚性梗阻性心肌病患者，这是一种计划性心肌梗死（PMI）的人类模型。在PMI之前和之后的不同时间间隔获得系列血液样本，接受选择性诊断性冠状动脉造影术的患者和自发性心肌梗死（SMI）患者分别作为阴性和阳性对照。我们确定了参与嘧啶代谢、三羧酸循环及其上游贡献者和戊糖磷酸途径的代谢物循环水平的变化。早在PMI后10分钟，在初始衍生组中就检测到多种代谢物水平的变化，并在第二个独立的PMI患者组中进行验证。由乌头酸、次黄嘌呤、氧化三甲胺和苏氨酸组成的PMI衍生代谢特征将SMI患者与接受诊断性冠状动脉造影术的患者区分开来，并且冠状窦采样将心脏衍生代谢变化与外周代谢变化区分开来。我们的研究结果确定了代谢谱在心肌损伤早期检测中的作用，并表明类似的方法可用于检测或预测其他疾病状态。
Emerging metabolomic tools have created the opportunity to establish metabolic signatures of myocardial injury. We applied a mass spectrometry-based metabolite profiling platform to 36 patients undergoing alcohol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of planned myocardial infarction (PMI). Serial blood samples were obtained before and at various intervals after PMI, with patients undergoing elective diagnostic coronary angiography and patients with spontaneous myocardial infarction (SMI) serving as negative and positive controls, respectively. We identified changes in circulating levels of metabolites participating in pyrimidine metabolism, the tricarboxylic acid cycle and its upstream contributors, and the pentose phosphate pathway. Alterations in levels of multiple metabolites were detected as early as 10 minutes after PMI in an initial derivation group and were validated in a second, independent group of PMI patients. A PMI-derived metabolic signature consisting of aconitic acid, hypoxanthine, trimethylamine N-oxide, and threonine differentiated patients with SMI from those undergoing diagnostic coronary angiography with high accuracy, and coronary sinus sampling distinguished cardiac-derived from peripheral metabolic changes. Our results identify a role for metabolic profiling in the early detection of myocardial injury and suggest that similar approaches may be used for detection or prediction of other disease states.