Abstract
Atrial fibrillation (AF) is an abnormal heart rhythm related to an increased risk of heart failure, dementia, and stroke. The distinction between valvular and non-valvular AF remains a debate. In this study, proteomics and metabolomics were integrated to describe the dysregulated metabolites and proteins of AF patients relative to sinus rhythm (SR) patients. Totally 47 up-regulated and 41 down-regulated proteins in valvular AF, and 59 up-regulated and 149 down-regulated proteins in non-valvular AF were recognized in comparison to SR patients. Moreover, 58 up-regulated and 49 significantly down-regulated metabolites in valvular AF, and 47 up-regulated and 122 down-regulated metabolites in persistent non-valvular AF patients were identified in comparison to SR patients. Based on analysis of differential levels of metabolites and proteins, 15 up-regulated and 22 down-regulated proteins, and 13 up-regulated and 122 down-regulated metabolites in persistent non-valvular AF were identified relative to valvular AF. KEGG pathway enrichment analysis showed the altered proteins and metabolites were significantly related to multiple metabolic pathways, such as Glycolysis/Gluconeogenesis. Interestingly, the enrichment pathways related to non-valvular AF were obviously different from those in valvular AF. For example, valvular AF was significantly related to Glycolysis/Gluconeogenesis, but non-valvular AF was more related to Citrate cycle (TCA cycle). Correlation analysis between the differentially expressed proteins and metabolites was also performed. Several hub proteins with metabolites were identified in valvular AF and non-valvular AF. For example, Taurine, D-Threitol, L-Rhamnose, and DL-lactate played crucial roles in valvular AF, while Glycerol-3-phosphate dehydrogenase, Inorganic pyrophosphatase 2, Hydroxymethylglutaryl-CoAlyase, and Deoxyuridine 5-triphosphate nucleotidohydrolase were crucial in non-valvular AF. Then two hub networks were recognized as potential biomarkers, which can effectively distinguish valvular AF and non-valvular persistent AF from SR samples, with areas under curve of 0.75 and 0.707, respectively. Hence, these metabolites and proteins can be used as potential clinical molecular markers to discriminate two types of AF from SR samples. In summary, this study provides novel insights to understanding the mechanisms of AF progression and identifying novel biomarkers for prognosis of non-valvular AF and valvular AF by using metabolomics and proteomics analyses.
Highlights
Atrial fibrillation (AF) is the most common arrhythmia with an abnormal atrial rhythm, resulting in increasing risk of heart failure, and stroke (Zhou et al, 2019)
Through metabolomic and proteomic analyses, we identified differential levels of proteins and metabolites in non-valvular AF and valvular AF compared to SR samples, and found the huge metabolic profiling differences between non-valvular AF and valvular AF
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed altered proteins and metabolites were significantly related to metabolic pathways
Summary
Atrial fibrillation (AF) is the most common arrhythmia with an abnormal atrial rhythm, resulting in increasing risk of heart failure, and stroke (Zhou et al, 2019). The AF-associated atrial electrical, and structural remodeling mechanisms are more complicated and variable in patients compared with other types of arrhythmia. Various heart diseases may lead to atrial remodeling, resulting in the development of AF, whereas AF can give rise to atrial remodeling due to the progression of others arrhythmia (Anne et al, 2005). Heart valve-related AF is most common in patients with rheumatic mitral stenosis, and the non-valvular related AF refers to the unclear etiology with no valvular heart disease (Fauchier et al, 2015). Despite a large number of basic and clinical studies, little is known about the basic mechanical difference between valvular and non-valvular AF. Identifying more reliable biomarkers for early diagnosis is urgent and can help understand the pathological mechanism of AF and provide new therapeutic targets
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