Label-free proteomic analysis of serum exosomes from paroxysmal atrial fibrillation patients

Abstract

Background Atrial fibrillation (AF) is the most common cardiac heterogeneous rhythm disorder. It represents a major cause of mortality and morbidity, mainly related to embolic events and heart failure. Mechanisms of AF are complex and remain incompletely understood. Recent evidence suggests exosomes are membrane-coated objects released by many cell-types. Their presence in body fluids and the variable surface composition and content render them attractive as a mechanism for potential biomarkers. However, the content of serum exosomes of AF patients has not been fully delineated. Methods In this work, the serum exosomes from AF patients and healthy donors were used to compare changes in the exosome protein content. Exosomes were isolated from serum of AF patients and healthy donors and their purity was confirmed by Western blotting assays and transmission electron microscopy (TEM). Label-free LC–MS/MS quantitative proteomic analysis was applied to analyze protein content of serum exosomes. Results A total of 440 exosomal protein groups were identified, differentially expressed proteins were filtrated with fold change ≥ 2.0 (AF/controls protein abundance ratio ≥ 2 or ≤ 0.5) and p value less than 0.05 (p < 0.05), significantly changed in abundance group contains 39 elevated proteins and 18 reduced proteins, while consistent presence/absence expression profile group contains 40 elevated proteins and 75 reduced proteins. Bioinformatic analysis of differential exosomal proteins confirmed the significant enrichment of components involved in the anticoagulation, complement system and protein folding. Parallel-Reaction Monitoring Relative Quantitative Analysis (PRM) further suggested that AF related to complement system and protein folding. Conclusions These results revealed the composition and potential function of AF serum exosomes, thus providing a new perspective on the complement system and protein folding to AF.

Exploration of Proteomics Analysis of Crop Milk in Pigeons (Columba livia) during the Lactation Period

“…Cellular protein synthesis consists of three distinct stages, initiation, elongation, and termination, and all stages depend on translation factors. 30 Herein, we speculate that ribosomal proteins in pigeon milk might be from the exfoliated crop epithelium and mainly participated in the synthesis of other pigeon milk proteins with biological functions. In addition to ribosomes, we also found the keratin, peroxiredoxin, annexin, and heat shock proteins were the main pigeon milk proteins.…”

“…In addition, our results indicated that eukaryotic translation initiation factor 2 and tRNA synthetase have a high degree of connectivity of ribosome. Cellular protein synthesis consists of three distinct stages, initiation, elongation, and termination, and all stages depend on translation factors . Herein, we speculate that ribosomal proteins in pigeon milk might be from the exfoliated crop epithelium and mainly participated in the synthesis of other pigeon milk proteins with biological functions.…”

Extracellular Vesicles in Atrial Fibrillation—State of the Art

“…Ni et al conducted a proteomic analysis of serum EVs comparing paroxysmal AF patients with healthy subjects. These two groups were proven to have different expression levels of many proteins mainly involved in anticoagulation, complement system, and protein folding, as indicated by the bioinformatic analysis [ 60 ]. Zietzer et al proved that patients suffering from AF had higher levels of large EVs derived from platelets in the left atrial appendage than patients with no AF.…”

Potential Applications and Functional Roles of Exosomes in Cardiometabolic Disease

“…These microbial communities may release EVs during the onset of myocardial injury, which, depending on their origin, could be enriched in MMP9 and elicit a protective role during plaque rupture [180]. Likewise, Ni et al characterized the protein profile of serum exosomes from atrial fibrillation patients and found 40 elevated proteins and 75 reduced proteins when compared to healthy controls [181]. Interestingly, these proteins were associated with anticoagulation, the complement system and protein folding.…”