Differential Expression, Interactive Relationship and Functional Pathway of Micro Ribonucleic Acids and Proteins in Plasma Exosomes of Patients with Atrial Fibrillation

Abstract

Background Atrial fibrillation (AF) is one of the most common arrhythmia all over the world with increased morbidity and mortality in the recent years. Micro ribonucleic acids (miRNAs) and proteins in plasma exosomes are a hot topic of mechanism analysis, liquid biopsy and drug delivery. For the first time worldwide, the current study was designed to analyze differential expression, interactive relationship and functional pathway of miRNAs and proteins in plasma exosomes of patients with AF. Methods The current study enrolled 24 individuals, including 8 individuals without AF, 8 patients with paroxysmal AF and 8 patients with persistent AF. Exosomes were extracted from plasma by ultracentrifugation and verified by transmission electron microscopy, western blot and nanoparticle tracking analyses. MiRNAs were dealt with MGIEasy Small RNA Library Prep Kit and analyzed by high-throughput sequencing platform BGISEQ-500. Proteins were labeled with Tandem Mass Tag Labeling Kit and analyzed by nanospray high performance liquid chromatography-mass spectrometry. Results All individuals had a mean age of 73.5±16.2 years, and 17 individuals were males (70.8%). Compared with individuals without AF, patients with paroxysmal AF had 263 downregulated and 535 upregulated known miRNAs, and patients with persistent AF had 164 downregulated and 676 upregulated known miRNAs. Compared with individuals without AF, patients with paroxysmal AF had 188 downregulated proteins and 4 upregulated proteins, and patients with persistent AF had 78 downregulated proteins and 6 upregulated proteins. Interactive analyses showed that compared with individuals without AF, both patients with paroxysmal and persistent AF had the top concentrated pathways of differential miRNAs and proteins were regulation of actin cytoskeleton, focal adhesion and platelet activation. Conclusions The current study detected plasma exosomes in patients with AF and displayed differential expression of miRNAs and proteins in plasma exosomes of these patients. Patients with AF have more upregulated miRNAs and more downregulated proteins in plasma exosomes than individuals without AF. Moreover, these differentially expressed miRNAs and proteins and their interactive relationship in plasma exosomes were related to regulation of actin cytoskeleton and other signaling pathways involved in AF. They could be key factors in the development and identification of AF and applied as preventative and therapeutic targets of AF. Further studies about AF are needed for more detailed pathways of miRNAs and proteins in exosomes and rapid development of exosome based therapies. Keywords atrial fibrillation, micro ribonucleic acid, plasma exosomes