Circulating proteomic patterns in AF related left atrial remodeling indicate involvement of coagulation and complement cascade

Abstract

BackgroundLeft atrial (LA) electro-anatomical remodeling and diameter increase in atrial fibrillation (AF) indicates disease progression and is associated with poor therapeutic success. Furthermore, AF leads to a hypercoagulable state, which in turn promotes the development of a substrate for AF and disease progression in the experimental setting. The aim of this study was to identify pathways associated with LA remodeling in AF patients using untargeted proteomics approach.MethodsPeripheral blood samples of 48 patients (62±10 years, 63% males, 59% persistent AF) undergoing AF catheter ablation were collected before ablation. 23 patients with left atrial low voltage areas (LVA), defined as <0.5 mV, and 25 patients without LVA were matched for age, gender and CHA2DS2-VASc score. Untargeted proteome analysis was performed using LC-ESI-Tandem mass spectrometry in a label free intensity based workflow. Significantly different abundant proteins were identified and used for pathway analysis and protein-protein interaction analysis.ResultsAnalysis covered 280 non-redundant circulating plasma proteins. The presence of LVA correlated with 30 differentially abundant proteins of coagulation and complement cascade (q<0.05).ConclusionsThis pilot proteomic study identified plasma protein candidates associated with electro-anatomical remodeling in AF and pointed towards an imbalance in coagulation and complement pathway, tissue remodeling and inflammation.

Interrelationship Between Inflammatory Biomarkers and Collagen Remodeling Proteins in Atrial Fibrillation

“…Although, in our studies, we have not addressed the dysregulation of coagulation and the complement system in relation to its contribution to the pathogenesis of AF, several previous reports have provided supportive data on the dysregulation of these processes which lead to tissue damage and a hypercoagulable state. 32 – 36 …”

“…Although, in our studies, we have not addressed the dysregulation of coagulation and the complement system in relation to its contribution to the pathogenesis of AF, several previous reports have provided supportive data on the dysregulation of these processes which lead to tissue damage and a hypercoagulable state. [32][33][34][35][36] Besides the electrophysiologic evaluation, imaging techniques such as MRI have become very useful in understanding the structural pathophysiology of AF. 37,38 The data on the collagen remodeling proteins and inflammatory biomarkers reported herein may have a complimentary role to the structural remodeling data obtained with imaging techniques.…”

Identification of Hub mRNAs and lncRNAs in Atrial Fibrillation Using Weighted Co-expression Network Analysis With RNA-Seq Data

“…A recent genetic study showed that genetic variation of interleukin-18 is related to a lower risk of atrial fibrillation among people in the Northeast China ( Wang et al, 2017 ). In addition, Kornej et al (2018) reported that complement and coagulation cascades were also related to AF. These reports, together with our findings, further prove the key role of these signals in AF.…”

Alterations in complement and coagulation pathways of human placentae subjected to in vitro fertilization and embryo transfer in the first trimester

“…[30] The major biological functions of these systems include defense against infections, connecting the innate and adaptive immunity, and the clearance of immune complexes and apoptotic cells. [31] The complement cascade, when activated by the classical, mannose-binding lectin, or alternative pathways, deposits several split products on the cell membrane, ultimately creating a cytotoxic cell lysis complex. [32] The complement split products also include free circulating anaphylatoxins such as C3a and C5a, which can initiate inflammation and tissue injury.…”