Investigation of novel metabolites potentially involved in the pathogenesis of coronary heart disease using a UHPLC-QTOF/MS-based metabolomics approach

Yiping Li,Yuejin Yang,Kefei Dou,Yuan He,Yang Wang,Changzhe Chen,Jielin Pu,Jingzhou Chen,Chenxi Song,Dong Zhang,Yanyan Zhao,Yinxiao Bai

doi:10.1038/s41598-017-15737-3

Yiping Li, Yuejin Yang + Show 10 more

Open Access

https://doi.org/10.1038/s41598-017-15737-3

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Abstract

Coronary heart disease (CHD) is associated with complex metabolic disorders, but its molecular aetiology remains unclear. Using a novel nontargeted metabolomics approach, we explored the global metabolic perturbation profile for CHD. Blood samples from 150 patients with severe obstructive CHD and 150 angiographically normal controls were collected. Metabolic fingerprinting was performed by ultra-high performance liquid chromatography coupled to quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS) technique. After adjusting for CHD traditional risk factors and metabolic batch, a comprehensive list of 105 metabolites was found to be significantly altered in CHD patients. Among the metabolites identified, six metabolites were discovered to have the strongest correlation with CHD after adjusting for multiple testing: palmitic acid (β = 0.205; p < 0.0001), linoleic acid (β = 0.133; p < 0.0001), 4-pyridoxic acid (β = 0.142; p < 0.0001), phosphatidylglycerol (20:3/2:0) (β = 0.287; p < 0.0001), carnitine (14:1) (β = 0.332; p < 0.0001) and lithocholic acid (β = 0.224; p < 0.0001); of these, 4-pyridoxic acid, lithocholic acid and phosphatidylglycerol (20:3/2:0) were, to the best of our knowledge, first reported in this study. A logistic regression model further quantified their positive independent correlations with CHD. In conclusion, this study surveyed a broad panel of nontargeted metabolites in Chinese CHD populations and identified novel metabolites that are potentially involved in CHD pathogenesis.

Highlights

Coronary heart disease (CHD) is one of the leading causes of mortality worldwide, but its pathogenic mechanism remains poorly understood
To explore alterations in the plasma metabolites that may be associated with CHD, two independent case-control groups were constructed based on strict coronary angiographic evidence: one group consisted of 150 CHD subjects, and one group consisted of 150 age- and gender-matched control subjects
Using a nontargeted metabolomics approach, we explored the molecular perturbation profile of patients with severe CHD compared with angiographically normal controls

Summary

Introduction

Coronary heart disease (CHD) is one of the leading causes of mortality worldwide, but its pathogenic mechanism remains poorly understood. It is well-known that CHD is linked with complex metabolic disorders, such as obesity, insulin resistance, and diabetes[1,2]. Certain circulating metabolites, such as homocysteine, cholesterol and triglycerides, have been recognized for decades as being strongly associated with CHD3–5 Beyond these well-known associations, researchers believe that there might still be many other dysregulated metabolites that have yet to be described. Targeted metabolite changes by examining the global plasma metabolomics profile of coronary heart disease and searching for new metabolites that are potentially involved in CHD pathogenesis

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