Systems characterization of differential plasma metabolome perturbations following thrombotic and non-thrombotic myocardial infarction

Publication date: 8 May 2017
Source:Journal of Proteomics, Volume 160
Author(s): Patrick J. Trainor, Bradford G. Hill, Samantha M. Carlisle, Eric C. Rouchka, Shesh N. Rai, Aruni Bhatnagar, Andrew P. DeFilippis
Myocardial infarction (MI) is an acute event characterized by myocardial necrosis. Thrombotic MI is caused by spontaneous atherosclerotic plaque disruption that results in a coronary thrombus; non-thrombotic MI occurs secondary to oxygen supply-demand mismatch. We sought to characterize the differential metabolic perturbations associated with these subtypes utilizing a systems approach. Subjects presenting with thrombotic MI, non-thrombotic MI and stable coronary artery disease (CAD) were included. Whole blood was collected at two acute time-points and at a time-point representing the quiescent stable disease state. Plasma metabolites were analyzed by untargeted UPLC-MS/MS and GC–MS. A weighted network was constructed, and modules were determined from the resulting topology. To determine perturbed modules, an enrichment analysis for metabolites that demonstrated between-group differences in temporal change across the disease state transition was then conducted.Biological significanceWe report evidence of metabolic perturbations of acute MI and determine perturbations specific to thrombotic MI. Specifically, a module characterized by elevated glucocorticoid steroid metabolites following acute MI showed greatest perturbation following thrombotic MI. Modules characterized by elevated pregnenolone metabolites, monoacylglycerols, and acylcarnitines were perturbed following acute MI. A module characterized by a decrease in plasma amino acids following thrombotic MI was differentially perturbed between MI subtypes.

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