Metabolic Disturbances Identified in Plasma Samples from ST-Segment Elevation Myocardial Infarction Patients

Hindawi Disease Markers Volume 2019, Article ID 7676189, 10 pages https://doi.org/10.1155/2019/7676189 Research Article Metabolic Disturbances Identified in Plasma Samples from ST-Segment Elevation Myocardial Infarction Patients Vânia Aparecida Mendes Goulart ,1 Anderson Kenedy Santos,1 Valéria Cristina Sandrim,2 Josimar Marques Batista,3 Mauro Cunha Xavier Pinto ,4 Luiz Cláudio Cameron ,5 and Rodrigo Ribeiro Resende 1 1 Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil 2 Instituto de Ensino e Pesquisa da Santa Casa de BH, Belo Horizonte, MG, Brazil 3 Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil 4 Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, GO, Brazil 5 Laboratório de Bioquímica de Proteínas, Centro de Inovação de Espectrometria de Massas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil Correspondence should be addressed to Vânia Aparecida Mendes Goulart; and Rodrigo Ribeiro Resende; Received 21 January 2019; Revised 7 May 2019; Accepted 16 May 2019; Published 1 July 2019 Guest Editor: Zhongjie Shi Copyright © 2019 Vânia Aparecida Mendes Goulart et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ST-segment elevation myocardial infarction (STEMI) is the most severe form of myocardial infarction (MI) and the main contributor to morbidity and mortality caused by MI worldwide. Frequently, STEMI is caused by complete and persistent occlusion of a coronary artery by a blood clot, which promotes heart damage. STEMI impairment triggers changes in gene transcription, protein expression, and metabolite concentrations, which grants a biosignature to the heart dysfunction. There is a major interest in identifying novel biomarkers that could improve the diagnosis of STEMI. In this study, the phenotypic characterization of STEMI patients (n = 15) and healthy individuals (n = 19) was performed, using a target metabolomics approach. Plasma samples were analyzed by UPLC-MS/MS (ultra-high-performance liquid chromatography-tandem mass spectrometry) and FIA-MS (MS-based flow injection analysis). The goal was to identify novel plasma biomarkers and metabolic signatures underlying STEMI. Concentrations of phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, and biogenic amines were altered in STEMI patients in relation to healthy subjects. Also, after multivariate analysis, it was possible to identify alterations in the glycerophospholipids, alpha-linolenic acid, and sphingolipid metabolisms in STEMI patients. 1. Introduction Myocardial infarction (MI) is a heart blood flow disruption that leads to tissue damage and cell death in the heart muscle. This pathology presents a high incidence worldwide, and it is a common cause of death and disability in humans [1]. MI has two major clinical manifestations: non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI), which is the more severe form and main contributor to morbidity and mortality by MI [2–4]. STEMI results from the abrupt occlusion of an epicardial coronary artery; as a consequence, the myocardium distal to the occlusion site becomes ischemic [5, 6]. During the ischemic process, oxygen supply is interrupted, and mitochondrial oxidative phosphorylation rapidly stops, with a massive reduction of ATP production from energy metabolism. A compensatory increase in anaerobic glycolysis for ATP production leads to the accumulation of hydrogen ions and lactate, resulting in intracellular acidosis and inhibition of glycolysis, as well as mitochondrial fatty 2 acid and residual energy metabolism. Impaired contraction with persistent electrical activity (excitation-contraction uncoupling) is developed in association with alterations in ion transport systems in the sarcolemma and organellar membranes [6–8]. In addition to the osmotic and ionic imbalance, the membrane depolarization also activates the voltage-dependent Ca2+ channels, raising levels of intracellular Ca2+. The rapid increase of intracellular calcium is due to the influx through the membrane and by the release of Ca2+ present in the mitochondria and in the cytoplasmic reticulum. Excessive cytosolic Ca2+ leads to the activation of calcium-dependent proteases, phospholipases, lipases, ATPases, and endonucleases. Activation of these enzymes alters cell function, destabilizes the structure of plasma membrane and cytoskeleton, increases lipolysis by free fatty acid metabolism, induces superoxide radical production, promotes DNA damage, and ultimately leads to cell death [9–12]. STEMI injury triggers changes in gene transcription, protein expression, and metabolite concentrations, which grant a biosignature of the heart dysfunction [13–15]. Detection of these biochemical changes has resulted in the discovery of emerging biomarkers, such as myoglobin, total creatine kinase (CK), CK-myocardial band, troponin I (cTnI), and troponin T (cTnT) [16]. However, the efficacy of these STEMI biomarkers is questionable because of the low sensitivity (35% for CK-MB and cTnI) and specificity (85 and 86% for CK-MB and cTnI, respectively) in the first 8 h after injury [15, 17]. The low sensitivity and specificity of biomarkers added to the fact that they can only be detected at least six hours after symptoms onset and that the MI diagnosis is based, besides other factors, in symptoms, that can vary individually, lay emphasis on the importance of the improvement of a biochemical diagnosis of MI [3, 5, 18]. The metabolomics approach has demonstrated great utility in the biomarker discovery field, as well as in detecting changes in biological pathways and in providing information on the mechanisms underlying various conditions, including cardiovascular diseases [19–21]. It is based on the global quantitative measurement of low molecular weight endogenous metabolites in tissues or biological fluids [22]. In this study, a target metabolomics approach was used to characterize the phenotypes of STEMI patients and healthy individuals. The overarching goal was to identify novel plasma biomarkers and metabolic signatures underlying STEMI. 2. Methods 2.1. Study Population. The study was conducted according to the Declaration of Helsinki, and its protocol was approved by the Ethics Committee in Research of Santa Casa Misericórdia of Belo Horizonte under number 064/2009. All subjects that agreed to participate prior to their inclusion in the study have signed an informed consent form. STEMI patients were screened based on the following inclusion criteria: age 4080 years, gender-balanced, chest pain above 20 minutes, and electrocardiographic (ECG) features consistent with STEMI: (...truncated)