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



We 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.
Department of Medicine, Division of Cardiovascular Medicine, University of Louisville, United States; Diabetes and Obesity Center, University of Louisville, United States.
Patrick J
PJ
Trainor
Department of Medicine, Division of Cardiovascular Medicine, University of Louisville, United States; Diabetes and Obesity Center, University of Louisville, United States.
Bradford G
BG
Hill
Department of Pharmacology and Toxicology, University of Louisville, United States.
Samantha M
SM
Carlisle
Department of Computer Engineering and Computer Science, University of Louisville, United States.
Eric C
EC
Rouchka
Department of Bioinformatics and Biostatistics, University of Louisville, United States.
Shesh N
SN
Rai
Department of Medicine, Division of Cardiovascular Medicine, University of Louisville, United States; Diabetes and Obesity Center, University of Louisville, United States.
Aruni
A
Bhatnagar
Department of Medicine, Division of Cardiovascular Medicine, University of Louisville, United States; Diabetes and Obesity Center, University of Louisville, United States; KentuckyOne/Jewish Hospital, United States; Johns Hopkins University, United States. Electronic address: APDeFi01@louisville.edu.
Andrew P
AP
DeFilippis
D000328:Adult; D000368:Aged; D001769:Blood / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D003328:Coronary Thrombosis / Q000150:complications*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005938:Glucocorticoids / Q000097:blood / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D050178:Monoglycerides / Q000097:blood / Q000378:metabolism; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D010101:Oxygen Consumption; D011284:Pregnenolone / Q000097:blood / Q000378:metabolism; D053719:Tandem Mass Spectrometry
D005938:Glucocorticoids; D050178:Monoglycerides; C116917:acylcarnitine; D011284:Pregnenolone; D002331:Carnitine
Coronary artery disease; Metabolomics; Myocardial infarction; Network analysis; Systems biology