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

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.

Fat, Sugar, Whole Grains and Heart Disease: 50 Years of Confusion

“…For example, a recent development is the recognition of lipoprotein subclasses [ 50 , 51 , 52 ]. Related to this is the use of metabolomics for the identification of diverse substances associated with CHD [ 53 ]. This line of investigation may lead to the identification of new biomarkers that can serve as valuable tools in CHD research.…”

Personalized Early-Warning Signals during Progression of Human Coronary Atherosclerosis by Landscape Dynamic Network Biomarker

“…In our result, PG (16:1/16:1) and PG (18:3/20:4) are DNB molecule candidates in 14 samples of the Stage A group (15 samples in total), which reveals the importance of PGs in the progression of coronary atherosclerosis, and their specific molecular mechanisms need to be further studied. Palmitic acid, a molecule involved in fatty acid metabolism, has been reported to be intimately related to cardiovascular disease [ 29 , 33 , 34 ]. The metabolic dynamic changes caused by palmitic acid intake can influence the levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, which show a strong positive correlation with the development of coronary heart disease [ 35 , 36 , 37 ].…”

Serum Lactate: Creatinine Ratio as a Prognostic Marker for Liver Failure Patients Treated by artificial liver support systems

“…Studies [6,[28][29][30] have shown that ALSSs therapy can remove harmful substances from the body, maintain homeostasis, temporarily assist or replace liver function, facilitate hepatocyte regeneration and recovery of liver function, and improve the survival rate of patients with liver failure. Hu P. [11] found that levels of ALB, creatinine, TBIL, INR, PTA, and ALT in serum changed signi cantly before and after ALSSs treatment. Hu S. et al [13] explored the curative effect of hybrid-bioarti cial liver on patients with liver failure related to infection by hepatitis B virus, and found that ALT, ALB, and TBIL were signi cantly altered after ALSSs treatment.…”

“…Metabonomics has developed rapidly over more than a decade, achieving great results in disease diagnosis, drug research and development, and other elds of human health care [10][11][12][13][14]. Yang L. et al adopted for metabolomics analysis a rat model in which liver failure was induced by application of tetrachloromethane and alpha-naphthylisothiocyanate.…”