Comprehensive Metabolic Profiling of Inflammation Indicated Key Roles of Glycerophospholipid and Arginine Metabolism in Coronary Artery Disease

Abstract

BackgroundSystemic immune inflammation is a key mediator in the progression of coronary artery disease (CAD), concerning various metabolic and lipid changes. In this study, the relationship between the inflammatory index and metabolic profile in patients with CAD was investigated to provide deep insights into metabolic disturbances related to inflammation.MethodsWidely targeted plasma metabolomic and lipidomic profiling was performed in 1,234 patients with CAD. Laboratory circulating inflammatory markers were mainly used to define general systemic immune and low-grade inflammatory states. Multivariable-adjusted linear regression was adopted to assess the associations between 860 metabolites and 7 inflammatory markers. Least absolute shrinkage and selection operator (LASSO) logistic-based classifiers and multivariable logistic regression were applied to identify biomarkers of inflammatory states and develop models for discriminating an advanced inflammatory state.ResultsMultiple metabolites and lipid species were linearly associated with the seven inflammatory markers [false discovery rate (FDR) <0.05]. LASSO and multivariable-adjusted logistic regression analysis identified significant associations between 45 metabolites and systemic immune-inflammation index, 46 metabolites and neutrophil–lymphocyte ratio states, 32 metabolites and low-grade inflammation score, and 26 metabolites and high-sensitivity C-reactive protein states (P < 0.05). Glycerophospholipid metabolism and arginine and proline metabolism were determined as key altered metabolic pathways for systemic immune and low-grade inflammatory states. Predictive models based solely on metabolite combinations showed feasibility (area under the curve: 0.81 to 0.88) for discriminating the four parameters that represent inflammatory states and were successfully validated using a validation cohort. The inflammation-associated metabolite, namely, β-pseudouridine, was related to carotid and coronary arteriosclerosis indicators (P < 0.05).ConclusionsThis study provides further information on the relationship between plasma metabolite profiles and inflammatory states represented by various inflammatory markers in CAD. These metabolic markers provide potential insights into pathological changes during CAD progression and may aid in the development of therapeutic targets.

Multinomial machine learning identifies independent biomarkers by integrated metabolic analysis of acute coronary syndrome

“…It can be biosynthesized from L-lysine and acetyl-CoA via the enzyme known as Lysine N-acetyltransferase or via the proteolytic degradation of Nacetylated proteins (often histones) by speci c hydrolases. There is proof that the histone acetylation product N6-acetyl-L-lysine is favorably correlated with atherogenesis and CAD risk [36,37]. In our study, N6-Acetyl-L-lysine was independent of conventional risk factors and positively correlated with coronary artery atherosclerotic plaque burden.…”

Persistent Inflammatory Lipotoxicity Impedes Pancreatic β-cell Function in Diet-Induced Obese Mice Despite Correction of Glucotoxicity

“…5B and 5F ). These findings are noteworthy since alterations in glycerophospholipid composition has been reported in several metabolic and inflammatory diseases [52, 53].…”

Prognostic implication of lipidomics in patients with coronary total occlusion undergoing PCI

“…Most glycerophosphates with long‐chain saturated fatty acids tend to be positively associated increased risk of atherosclerosis, 31 which could result in HDL surface rigidity and affect the uptake of cholesterol from peripheral tissues. 32 It has been implied that glycerophospholipids were associated with immunometabolism and chronic low‐grade inflammation, 33 , 34 which were predisposing factors of endothelial dysfunction and plaque disruption. Hence, lipid species could be the link among atherosclerosis, inflammation and acute cardiovascular events.…”

“…The logistic regression model is adjusted for hypertension and in-stent CTO HDL surface rigidity and affect the uptake of from peripheral tissues. 32 It has been implied that glycerophospholipids were associated with immunometabolism and chronic low-grade inflammation, 33,34 atherosclerosis, inflammation and acute cardiovascular events. Lipidomic analysis identified lipid elements related to increased risk of MACEs, implying structural features within lipid species, independent of traditional lipid-associated parameters, played an important role in the homeostasis of artery plaques.…”