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Differential Network Analysis Reveals Metabolic Determinants Associated with Mortality in Acute Myocardial Infarction Patients and Suggests Potential Mechanisms Underlying Different Clinical Scores Used To Predict Death.
Journal of Proteome Research ( IF 4.4 ) Pub Date : 2020-01-03 , DOI: 10.1021/acs.jproteome.9b00779
Alessia Vignoli 1, 2 , Leonardo Tenori 1, 2, 3 , Betti Giusti 3, 4, 5 , Serafina Valente 3, 4, 5 , Nazario Carrabba 6 , Daniela Balzi 7 , Alessandro Barchielli 7 , Niccolò Marchionni 3 , Gian Franco Gensini 8 , Rossella Marcucci 3, 4, 5 , Anna Maria Gori 3, 4, 5 , Claudio Luchinat 1, 2, 9 , Edoardo Saccenti 10
Affiliation  

We present here the differential analysis of metabolite-metabolite association networks constructed from an array of 24 serum metabolites identified and quantified via nuclear magnetic resonance spectroscopy in a cohort of 825 patients of which 123 died within 2 years from acute myocardial infarction (AMI). We investigated differences in metabolite connectivity of patients who survived, at 2 years, the AMI event, and we characterized metabolite-metabolite association networks specific to high and low risks of death according to four different risk parameters, namely, acute coronary syndrome classification, Killip, Global Registry of Acute Coronary Events risk score, and metabolomics NOESY RF risk score. We show significant differences in the connectivity patterns of several low-molecular-weight molecules, implying variations in the regulation of several metabolic pathways regarding branched-chain amino acids, alanine, creatinine, mannose, ketone bodies, and energetic metabolism. Our results demonstrate that the characterization of metabolite-metabolite association networks is a promising and powerful tool to investigate AMI patients according to their outcomes at a molecular level.

中文翻译:

差异网络分析揭示了急性心肌梗死患者死亡率相关的代谢决定因素,并提出了潜在的机制来预测死亡的不同临床评分。

我们在这里介绍了代谢物-代谢物关联网络的差异分析,该网络由24种血清代谢物组成,并通过核磁共振波谱对825名患者进行了鉴定,其中123名患者在2年内因急性心肌梗死(AMI)死亡。我们调查了在2年后发生AMI事件的患者中代谢物连通性的差异,并根据四种不同的风险参数,即急性冠脉综合征分类,Killip,对特定于高死亡风险和低死亡风险的代谢物-代谢物关联网络进行了表征。 ,急性冠脉事件全球注册风险评分和代谢组学NOESY RF风险评分。我们显示了几种低分子量分子在连接方式上的显着差异,暗示有关支链氨基酸,丙氨酸,肌酸酐,甘露糖,酮体和能量代谢的几种代谢途径的调节存在差异。我们的结果表明,代谢物-代谢物关联网络的表征是根据分子水平的结果调查AMI患者的有前途且有力的工具。
更新日期:2020-01-21
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