Association of Coronary Artery Disease and Metabolic Syndrome: Usefulness of Serum Metabolomics Approach

Jing, Ziwei; Liu, Liwei; Shi, Yingying; Du, Qianming; Zhang, Dingding; Zuo, Li; Du, Shouying; Zhi, Sun; Zhang, Xiaojian

doi:10.3389/fendo.2021.692893

Cited by 10 publications

(7 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the significant increases in the serum level of uracil observed in this study suggest that many biochemical reactions in the experimental group were triggered, possibly owing to metabolic disorders, and increased cellular oxidative stress. These results were inconsistent with those of previous studies, which showed decreases in serum concentration of uracil in patients with both coronary artery disease and MetS 47 . The discrepancy may be due to different factors leading to uracil metabolism; further research is needed to explore these differences.…”

Section: Discussioncontrasting

confidence: 89%

See 1 more Smart Citation

Impact of a long‐term high‐fructose diet on systemic metabolic profiles of mice

Wang

Han

et al. 2022

FASEB BioAdvances

View full text Add to dashboard Cite

Evidence is mounting that chronic high‐fructose diets (HFrD) can lead to metabolic abnormalities and cause a variety of diseases. However, the underlying mechanism by which long‐term high fructose intake influencing systemic metabolism remains unclarified. This study, therefore, attempted to investigate the impact of a high‐fructose diet on metabolic profile. Four‐week‐old male C57BL/6 mice were fed with 15% fructose solution as their only source of water for 8 weeks. Afterward, gas chromatography–mass spectrometry (GC–MS) was employed to investigate the comprehensive metabolic profile of serum, muscle, liver, heart, white adipose, brain, and kidney tissues, and multivariate analyses including principal component analysis (PCA) and orthogonal partial least squared‐discriminant analysis (OPLS‐DA) were applied to screen for differential metabolite expression between the HFrD and control groups. Furthermore, the MetaboAnalyst 5.0 ( http://www.metaboanalyst.ca ) and Kyoto Encyclopedia of Genes and Genomes database (KEGG; http://www.kegg.jp ) were employed to portray a detailed metabolic network. This study identified 62 metabolites related to HFrD and 10 disturbed metabolic pathways. The results indicated that high fructose intake mainly influenced amino acid metabolism and biosynthesis (glycine, serine, and threonine metabolism; aspartate, and glutamate metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis, and arginine biosynthesis pathways), glutathione metabolism, sphingolipid metabolism, and glyoxylate and dicarboxylate metabolism in serum, whereas these pathways were suppressed in the brain. Starch and sucrose metabolism in muscle was also disrupted. These results elucidate the effects of long‐term high fructose consumption on the metabolic profiles of various tissues and provide new insight for the identification of potential metabolic biomarkers and pathways disrupted by high fructose.

show abstract

Section: Discussioncontrasting

confidence: 89%

“…These results were inconsistent with those of previous studies, which showed decreases in serum concentration of uracil in patients with both coronary artery disease and MetS. 47 The discrepancy may be due to different factors leading to uracil metabolism; further research is needed to explore these differences.…”

Section: Discussioncontrasting

confidence: 84%

Impact of a long‐term high‐fructose diet on systemic metabolic profiles of mice

Wang

Han

et al. 2022

FASEB BioAdvances

View full text Add to dashboard Cite

show abstract

“…It was consistent with recent studies that increased levels of 2-(dimethylamino) guanosine and β-pseudouridine levels were related to incident heart failure and LV remodeling [ 45 , 46 ]. Furthermore, 2-(dimethylamino) guanosine has been linked to increased risk of coronary artery calcium [ 47 ] and all-cause mortality in diabetes [ 48 ], and elevated circulating levels of β-pseudouridine were associated with atrial fibrillation [ 49 ], heart failure [ 50 ] and CAD [ 51 ]. Here we report for the first time that β-pseudouridine was also a metabolic marker for the risks of death and MACE in CAD.…”

Section: Discussionmentioning

confidence: 99%

Plasma metabolomics provides new insights into the relationship between metabolites and outcomes and left ventricular remodeling of coronary artery disease

et al. 2022

View full text Add to dashboard Cite

Background Coronary artery disease (CAD) is a metabolically perturbed pathological condition. However, the knowledge of metabolic signatures on outcomes of CAD and their potential causal effects and impacts on left ventricular remodeling remains limited. We aim to assess the contribution of plasma metabolites to the risk of death and major adverse cardiovascular events (MACE) as well as left ventricular remodeling. Results In a prospective study with 1606 Chinese patients with CAD, we have identified and validated several independent metabolic signatures through widely-targeted metabolomics. The predictive model respectively integrating four metabolic signatures (dulcitol, β-pseudouridine, 3,3ʹ,5-Triiodo-l-thyronine, and kynurenine) for death (AUC of 83.7% vs. 76.6%, positive IDI of 0.096) and metabolic signatures (kynurenine, lysoPC 20:2, 5-methyluridine, and l-tryptophan) for MACE (AUC of 67.4% vs. 59.8%, IDI of 0.068) yielded better predictive value than trimethylamine N-oxide plus clinical model, which were successfully applied to predict patients with high risks of death (P = 0.0014) and MACE (P = 0.0008) in the multicenter validation cohort. Mendelian randomisation analysis showed that 11 genetically inferred metabolic signatures were significantly associated with risks of death or MACE, such as 4-acetamidobutyric acid, phenylacetyl-l-glutamine, tryptophan metabolites (kynurenine, kynurenic acid), and modified nucleosides (β-pseudouridine, 2-(dimethylamino) guanosine). Mediation analyses show that the association of these metabolites with the outcomes could be partly explained by their roles in promoting left ventricular dysfunction. Conclusions This study provided new insights into the relationship between plasma metabolites and clinical outcomes and its intermediate pathological process left ventricular dysfunction in CAD. The predictive model integrating metabolites can help to improve the risk stratification for death and MACE in CAD. The metabolic signatures appear to increase death or MACE risks partly by promoting adverse left ventricular dysfunction, supporting potential therapeutic targets of CAD for further investigation. Graphical Abstract

show abstract

“…N e w l y d e v e l o p e d metabolic profiling allows for the integrative analysis of small molecules under physiological or pathological conditions (18,19). The metabolomics capable of predicting cardiovascular diseases like atherosclerosis (16,17,21,22,(37)(38)(39)(40)(41)(42)(43)(44), dyslipidemia (45), and hypertension (46) has gradually come to the fore of research. In a large European cohort study consisting of 10,741 patients without CHD, there was a significant association between 5 phosphatidylcholines and an increased risk of CHD incidence, and there was comparable discrimination with classic risk factors (38).…”

Section: Discussionmentioning

confidence: 99%

The impact of hypertension for metabolites in patients with acute coronary syndrome

Feng¹,

Yu²,

Zong³

et al. 2023

Ann Transl Med

View full text Add to dashboard Cite

Background Acute coronary syndrome (ACS) is one of the leading causes of death and is often accompanied by hypertension. Methods We investigated whether hypertension affects the metabolism of patients with ACS. Serum samples were provided from healthy controls (HCs; n=26), patients with ACS (n=20), or those patients with ACS complicated with hypertension (HTN, n=21), and all were subjected to non-targeted metabolomics analyses based on gas chromatography-mass spectrometry (GC/MS). Differential metabolites were screened using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA). Kyoto Encyclopedia of Genes and Genomes (KEGG) provided metabolic pathways related to these metabolites. Results Compared to those in the HC group, 12 metabolites were significantly upregulated and 6 significantly downregulated in the ACS group; among these, L-cystine and isocitric acid showed the most obvious differences, respectively. Compared to those in the ACS group, 3 metabolites were significantly upregulated and 2 metabolites were significantly downregulated in the ACS-HTN group, among which oleic acid and chenodeoxycholic acid showed the most marked difference, respectively. The five most prominent metabolic pathways involved in differential metabolites between the ACS and HC groups were arginine biosynthesis; oxidative phosphorylation; alanine, aspartate and glutamate metabolism; citrate cycle; and glucagon signaling pathway. The metabolic pathways between the ACS and ACS-HTN groups were steroid biosynthesis, fatty acid biosynthesis, arginine biosynthesis, primary bile acid biosynthesis, and tyrosine metabolism. Conclusions A comprehensive study of the changes in circulatory metabolomics and the influence of HTN was conducted in patients with ACS. A serum metabolomics test can be used to identify differentially metabolized molecules and allow the classification of patients with ACS or those complicated with HTN.

show abstract

Association of Coronary Artery Disease and Metabolic Syndrome: Usefulness of Serum Metabolomics Approach

Cited by 10 publications

References 42 publications

Impact of a long‐term high‐fructose diet on systemic metabolic profiles of mice

Impact of a long‐term high‐fructose diet on systemic metabolic profiles of mice

Plasma metabolomics provides new insights into the relationship between metabolites and outcomes and left ventricular remodeling of coronary artery disease

The impact of hypertension for metabolites in patients with acute coronary syndrome

Contact Info

Product

Resources

About