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Untargeted metabolomic analysis of coronary artery disease patients with diastolic dysfunction show disturbed oxidative pathway

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Abstract

Introduction

Left ventricular diastolic dysfunction (LVDD) is common in patients with coronary artery disease (CAD) with prevalence estimates of 34% and constitutes a predictor of all-cause mortality. Although diastolic dysfunction is induced by myocardial ischemia and has been shown to alter the clinical course, the role of coronary artery disease in the diastolic dysfunction and its progression into heart failure has not been completely elucidated.

Objective

The present study was conducted to identify possible metabolites in coronary artery disease patients that are differentially regulated in patients with diastolic dysfunction.

Methods

The serum of CAD (n = 75) patients and young healthy volunteers (n = 43) were analysed by using gas chromatography mass spectrometry (GC–MS) technique. Pre-processing of data results in 1547 features; among them 1064 features were annotated using NIST library.

Results and Conclusion

Fifteen metabolites were found to be statistically different between cases and control. Variation in metabolites were identified and correlated with several clinically important echocardiography parameters i.e. LVDD grades, ejection fraction (EF) and E/e’ values. The results suggested that metabolic products of fatty acid oxidation and glucose oxidation pathways such as oleic acid, stearic acid, palmitic acid, linoleic acid, galactose, pyruvic and lactic acids are predominantly up regulated in patients with coronary artery disease and severity of diastolic dysfunction appears to be linked to increase in fatty acid oxidation and inflammation. The metabolic fingerprints of these patients give us an insight into the pathophysiological mechanism of diastolic dysfunction in coronary artery disease patients although it did not identify validated novel markers.

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Acknowledgements

We are thankful to Aga Khan University Hospital and South City Hospital cardiologists and cardiothoracic surgeons for their invaluable work in patient’s recruitment, samples and data collection. We also acknowledged the PAS (Pakistan Academy of Sciences) for granting funds to carry out this research work (Grant # 5-9/PAS/745).

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Authors

Contributions

SGM: study design, experimental design, data analysis, results interpretation and manuscript writing. TF: patient recruitment, samples and patients case history collection, data analysis, interpretation and manuscript writing. SH: study design, patient’s recruitment, data collection, samples collection, results interpretation and manuscript writing. AI: data analysis, results interpretation and manuscript writing. AJS: experimental guidance, data analysis and interpretation. SAS: clinical examination of CABG patients, recruitment and results interpretation. NB: clinical examination, echocardiography and results interpretation. SSB: echocardiography and results interpretation. HS: clinical examination of CABG patients, recruitment and results interpretation. MIC: experimental facilities. AR: experimental work facilities. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Syed Ghulam Musharraf.

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The authors have no relationships with industry to report and have no conflict of interest including financial, personal, political interest in this study.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Fatima, T., Hashmi, S., Iqbal, A. et al. Untargeted metabolomic analysis of coronary artery disease patients with diastolic dysfunction show disturbed oxidative pathway. Metabolomics 15, 98 (2019). https://doi.org/10.1007/s11306-019-1559-5

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