Biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study.

Background: Mitral valve disease (MVD)-associated atrial fibrillation (AF) is one of the most common arrhythmias with an increased risk of thromboembolic events. This study aimed to identify the molecular mechanisms and possible biomarkers for chronic AF in MVD by using multi-omics methods.

Methods: This prospective study enrolled patients with MVD (n=100) undergoing mitral valve replacement surgery. The patients were allocated into chronic AF and sinus rhythm (SR) groups. Plasma samples were collected preoperatively. Proteomics was performed with isobaric tags for relative and absolute quantitation (iTRAQ) to identify differential proteins (DPs) between the two groups. The selected DPs were then validated in a new cohort of patients by enzyme-linked immunosorbent assay (ELISA). A gas chromatography-mass spectrometer was used in the metabolomics study to identify differential metabolites (DMs). Bioinformatics analyses were performed to analyze the results.

Results: Among the 447 plasma proteins and 322 metabolites detected, 57 proteins and 55 metabolites, including apolipoprotein A-I (ApoA-I), apolipoprotein A-II (ApoA-II), LIM domain only protein 7 (LMO7), and vitronectin (VN) were differentially expressed between AF and SR patients. Bioinformatics analyses identified enriched pathways related to AF, including peroxisome proliferator-activated receptor alpha (PPARα), the renin angiotensin aldosterone system (RAAS), galactose, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism.

Conclusions: Using integrated multi-omics technologies in MVD-associated AF patients, the present study, for the first time, revealed important signaling pathways, such as PPARα, as well as possible roles of other signaling pathways, including the RAAS and galactose metabolism to understand the molecular mechanism of MVD-associated AF. It also identified a large number of DPs and DMs. Some identified proteins and metabolites, such as ApoA-I, ApoA-II, LMO7, and VN, may be further developed as biomarkers for MVD-associated AF.