Extracellular vesicles from epicardial fat mediate long-distance heart-brain communication and promote atrial fibrillation associated cognitive impairment (EAT exosomal miRNA-seq and hippocampal mRNA-seq)

2 weeks of rapid atrial pacing increased the release of epicardial adipose tissue (EAT) exosomes. The red fluorescence of Ad-CD63-RFP traces the increase of EAT exosomes in the canine hippocampus. RNA Sequencing showed that the differentially expressed genes of cfa-miR-22e in EAT exosomes were significantly increased, and its target gene of IL33 was down-regulated in the hippocampus. Exosomes secreted by EAT in AF model canine penetrate the BBB, and activate hippocampal microglia through cfa-miR-22e/IL33 signaling pathway, which may be related to the increased risk of cognitive impairment in AF. Overall design: To investigate the effect of atrial fibrillation on cognitive impairment, canines were randomly divided into the sham group, the pacing group. The miRNA was detected from EAT exosomes of canines in the sham group and the pacing group, and the mRNA was detected from hippocampal tissue in the same group of canines. The results of heart and brain sequencing were analyzed jointly