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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
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Copyright
© 2020 Published by Elsevier Inc.