Urine Metabolites Changes in Acute Myocardial Infarction Rats via Metabolomic Analysis

Abstract

ObjectiveTo screen biomarkers for forensic identification of acute myocardial infarction （AMI） by non-targeted metabolomic studies on changes of urine metabolites in rats with AMI.MethodsThe rat models of the sham surgery group, AMI group and hyperlipidemia + acute myocardial infarction （HAMI） group were established. Ultra-high performance liquid chromatography-mass spectrometry （UPLC-MS） was used to analyze the changes of urine metabolic spectrometry in AMI rats. Principal component analysis, partial least squares-discriminant analysis, and orthogonal partial least squares-discriminant analysis were used to screen differential metabolites. The MetaboAnalyst database was used to analyze the metabolic pathway enrichment and access the predictive ability of differential metabolites.ResultsA total of 40 and 61 differential metabolites associated with AMI and HAMI were screened, respectively. Among them, 22 metabolites were common in both rat models. These small metabolites were mainly concentrated in the niacin and nicotinamide metabolic pathways. Within the 95% confidence interval, the area under the curve （AUC） values of receiver operator characteristic curve for N8-acetylspermidine, 3-methylhistamine, and thymine were greater than 0.95.ConclusionN8-acetylspermidine, 3-methylhistamine, and thymine can be used as potential biomarkers for AMI diagnosis, and abnormal metabolism in niacin and nicotinamide may be the main causes of AMI. This study can provide reference for the mechanism and causes of AMI identification.

Keywords

• forensic pathology
• non-targeted metabolomics
• acute myocardial infarction
• ultra-high performance liquid chromatography-mass spectrometry （uplc-ms）
• rats
• urine