The N-Glycosylation of Total Plasma Proteins and IgG in Atrial Fibrillation

Abstract

Atrial fibrillation is a disease with a complex pathophysiology, whose occurrence and persistence are caused not only by aberrant electrical signaling in the heart, but by the development of a susceptible heart substrate. These changes, such as the accumulation of adipose tissue and interstitial fibrosis, are characterized by the presence of inflammation. N-glycans have shown great promise as biomarkers in different diseases, specifically those involving inflammatory changes. To assess the changes in the N-glycosylation of the plasma proteins and IgG in atrial fibrillation, we analyzed the N-glycosylation of 172 patients with atrial fibrillation, before and six months after a pulmonary vein isolation procedure, with 54 cardiovascularly healthy controls. An analysis was performed using ultra-high-performance liquid chromatography. We found one oligomannose N-glycan structure from the plasma N-glycome and six IgG N-glycans, mainly revolving around the presence of bisecting N-acetylglucosamine, that were significantly different between the case and control groups. In addition, four plasma N-glycans, mostly oligomannose structures and a derived trait that was related to them, were found to be different in the patients who experienced an atrial fibrillation recurrence during the six-month follow-up. IgG N-glycosylation was extensively associated with the CHA2DS2-VASc score, confirming its previously reported associations with the conditions that make up the score. This is the first study looking at the N-glycosylation patterns in atrial fibrillation and warrants further investigation into the prospect of glycans as biomarkers for atrial fibrillation.

Pathophysiology of Atrial Fibrillation and Approach to Therapy in Subjects Less than 60 Years Old

“…Although data on precise mechanistic pathways for diabetes mellitus (DM) remain limited, studies suggest that electrical and cardiac remodeling along with hyperglycemiainduced fibrotic change likely contribute to increased AF susceptibility. N-glycosylation involves the co-and post-translational addition of complex oligosaccharide structures (glycans) to proteins, influencing their structure, function, and processing, and are crucial for many biological processes, including cell signaling and recognition [26]. Recently, it has been shown that semaglutide, a glucagon-like peptide-1 receptor agonist that reduces the risk of adverse cardiovascular events in patients with diabetes, can lessen the cardiovascular risk associated with overweight and obese patients in the absence of diabetes as well [27].…”

Recent advances in N-glycan biomarker discovery among human diseases

“…A recent study comparing 316 CAD-and 156 CAD+ patients revealed differences in IgG N-glycan composition, showing that sialylated N-glycan structures negatively correlate with CAD [183]. In addition, IgG N-glycans have shown potential as biomarkers for atrial fibrillation (AF), a condition resulting from both abnormal electrical signalling in the heart and a susceptible heart substrate [184]. Specifically, AF patients were found to have higher levels of plasma and IgG oligomannose and lower levels of IgG bisecting GlcNAc than controls.…”

Anastrozole and Tamoxifen Impact on IgG Glycome Composition Dynamics in Luminal A and Luminal B Breast Cancers

“…Additionally, glycans lacking core fucose have been reported to display pro-inflammatory effects, potentially triggering antibody-dependent cellular cytotoxicity [5]. The glycosylation of IgG changes based on physiological conditions, few examples being ageing [6], sex hormone influence [7], and changes in lifestyle factors such as changes in body weight [8] and pathophysiological states, including rheumatoid arthritis [9], diabetes [10], cancers [11], cardiovascular diseases [12], infectious diseases [13], among others. Glycans are highly stable within individuals (intraindividual stability), and the observed changes in pathological conditions make them potential candidates as diagnostic and prognostic biomarkers.…”