Comprehensive metabolomic and proteomic analyses reveal candidate biomarkers and related metabolic networks in atrial fibrillation

Abstract

IntroductionAtrial fibrillation (AF) is an abnormal heart rhythm characterized by an irregular beating of the atria and is associated with an increased risk of heart failure, dementia, and stroke. Currently, the perturbation of plasma content due to AF disease onset is not well known.ObjectivesTo investigate dysregulated molecules in blood plasma of untreated AF patients, with the goal of identifying biomarkers for disease screening and pathological studies.MethodsLC-MS based untargeted metabolomics, lipidomics and proteomics analyses were performed to find candidate biomarkers. A targeted quantification assay and an ELISA were performed to validate the results of the omics analyses.ResultsWe found that 24 metabolites, 16 lipids and 16 proteins were significantly dysregulated in AF patients. Pathway enrichment analysis showed that the purine metabolic pathway and fatty acid metabolism were perturbed by AF onset. FA 20:2 and FA 22:4 show great linear correlational relationship with the left atrial area and could be considered for AF disease stage monitoring or prognosis evaluation.Conclusionwe used a comprehensive multiple-omics strategy to systematically investigate the dysregulated molecules in the plasma of AF patients, thereby revealing potential biomarkers for diagnosis and providing information for pathological studies.