Plasma metabolomics reveals a potential panel of biomarkers for early diagnosis in acute coronary syndrome

Abstract

Discovery of new biomarkers is critical for early diagnosis of acute coronary syndrome (ACS). Recent advances in metabolomic technologies have drastically enhanced the possibility of improving the knowledge of its physiopathology through the identification of the altered metabolic pathways. In this study, analyses of peripheral plasma from non-ST segment elevation ACS patients and healthy controls by gas chromatography-mass spectrometry (GC-MC) permitted the identification of 15 metabolites with statistical differences (p < 0.05) between experimental groups. Additionally, validation by GC-MC and liquid chromatography-MC permitted us to identify a potential panel of biomarkers formed by 5-OH-tryptophan, 2-OH-butyric acid and 3-OH-butyric acid. This panel of biomarkers reflects the oxidative stress and the hypoxic state that suffers the myocardial cells and consequently constitutes a metabolomic signature of the atherogenesis process that could be used for early diagnosis of ACS.

Keywords: Acute coronary syndrome; Biomarker; Metabolite; Metabolomics.

Fig. 1

Protocols for metabolomic analysis of plasma profiling (a) and fatty acids profiling (b) with a representative chromatogram including the identified metabolites summarized in Table 2a, c respectively

Fig. 2

Results of PCA for plasma metabolomic analysis (a) and plasma fatty acid analysis (b). In the score plot, healthy controls (left, blue) and NSTEACS patients (right, red) are represented (Color figure online)

Fig. 3

5-OH-tryptophan (21.292 min) showed decreased levels in NSTEACS patients compared to healthy controls (a). 2-OH-butyric acid (7.969 min) and 3-OH-butyric acid (8.734 min) showed increased plasma levels in NSTEACS patients compared to healthy controls (b)

Fig. 4

Validation results by GC/MS (a) and SRM (b). The three metabolites showed statistically significant changes between the two experimental groups