Plasma fingerprinting with GC-MS in acute coronary syndrome

Pharmacy Faculty, San Pablo-CEU University Madrid, Campus Montepríncipe, Boadilla del Monte, 28668 Madrid, Spain.
Analytical and Bioanalytical Chemistry (Impact Factor: 3.44). 02/2009; 394(6):1517-24. DOI: 10.1007/s00216-009-2610-6
Source: PubMed


New biomarkers of cardiovascular disease are needed to augment the information obtained from traditional indicators and to illuminate disease mechanisms. One of the approaches used in metabolomics/metabonomics for that purpose is metabolic fingerprinting aiming to profile large numbers of chemically diverse metabolites in an essentially nonselective way. In this study, gas chromatography-mass spectrometry was employed to evaluate the major metabolic changes in low molecular weight plasma metabolites of patients with acute coronary syndrome (n = 9) and with stable atherosclerosis (n = 10) vs healthy subjects without significant differences in age and sex (n = 10). Reproducible differences between cases and controls were obtained with pattern recognition techniques, and metabolites accounting for higher weight in the classification have been identified through their mass spectra. On this basis, it seems inherently plausible that even a simple metabolite profile might be able to offer improved clinical diagnosis and prognosis, but in addition, specific markers are being identified.

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    • "In this investigation, we initiated an effort to establish a mass spectrometry-based metabolomic analytical platform to characterize and to validate potential metabolic markers in heart failure, particularly in plasma due to its less-invasiveness nature compared to biopsy [36]; also its circulating nature enables us to obtain a temporal physiologic status of the patients [37]. 19 metabolites were chosen based on their demonstrated functions in the relevant biological processes to heart failure, specifically participating in the regulation of extracellular matrix remodeling [38], energy metabolism [39-41], inflammation [42], insulin resistance [43], renal dysfunction [44], and cardioprotection [45]. "
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    ABSTRACT: Heart failure is a multifactorial disease associated with staggeringly high morbidity and motility. Recently, alterations of multiple metabolites have been implicated in heart failure; however, the lack of an effective technology platform to assess these metabolites has limited our understanding on how they contribute to this disease phenotype. We have successfully developed a new workflow combining specific sample preparation with tandem mass spectrometry that enables us to extract most of the targeted metabolites. 19 metabolites were chosen ascribing to their biological relevance to heart failure, including extracellular matrix remodeling, inflammation, insulin resistance, renal dysfunction, and cardioprotection against ischemic injury. In this report, we systematically engineered, optimized and refined a protocol applicable to human plasma samples; this study contributes to the methodology development with respect to deproteinization, incubation, reconstitution, and detection with mass spectrometry. The deproteinization step was optimized with 20% methanol/ethanol at a plasma:solvent ratio of 1:3. Subsequently, an incubation step was implemented which remarkably enhanced the metabolite signals and the number of metabolite peaks detected by mass spectrometry in both positive and negative modes. With respect to the step of reconstitution, 0.1% formic acid was designated as the reconstitution solvent vs. 6.5 mM ammonium bicarbonate, based on the comparable number of metabolite peaks detected in both solvents, and yet the signal detected in the former was higher. By adapting this finalized protocol, we were able to retrieve 13 out of 19 targeted metabolites from human plasma. We have successfully devised a simple albeit effective workflow for the targeted plasma metabolites relevant to human heart failure. This will be employed in tandem with high throughput liquid chromatography mass spectrometry platform to validate and characterize these potential metabolic biomarkers for diagnostic and therapeutic development of heart failure patients.
    Clinical Proteomics 07/2013; 10(1):7. DOI:10.1186/1559-0275-10-7
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    • "This is not a trivial issue and prior to embarking on the task of discovering metabolic biomarkers, sufficiently sensitive and selective instruments and extensive compound libraries for metabolite identification should be available [35], while certain expertise in data analysis and interpretation will be necessary. One of the few metabolomic studies in the field of CVD involved a comparison of the metabolomic fingerprint obtained by GC-MS of plasma samples from non-STsegment elevation acute coronary syndrome (NSTEACS) patients, stable atherosclerosis patients and healthy patients [36] "
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    ABSTRACT: Metabolomics involves the identification and quantification of metabolites present in a biological system. Three different approaches can be used: metabolomic fingerprinting, metabolic profiling, and metabolic footprinting, in order to evaluate the clinical course of a disease, patient recovery, changes in response to surgical intervention or pharmacological treatment, as well as other associated features. Characteristic patterns of metabolites can be revealed that broaden our understanding of a particular disorder. In the present paper, common strategies and analytical techniques used in metabolomic studies are reviewed, particularly with reference to the cardiovascular field.
    BioMed Research International 01/2011; 2011:790132. DOI:10.1155/2011/790132 · 2.71 Impact Factor
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    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.
    Metabolomics 06/2013; 10(3). DOI:10.1007/s11306-013-0595-9 · 3.86 Impact Factor
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