AFibOmics Browser
Transcriptome and Proteome Mapping in the Sheep Atria Reveal Molecular Features of Atrial Fibrillation Progression
Abstract
Atrial fibrillation is a progressive cardiac arrhythmia that increases the risk of hospitalization and adverse cardiovascular events. There is a clear demand for more inclusive and large-scale approaches to understand the molecular drivers responsible for atrial fibrillation, as well as the fundamental mechanisms governing the transition from paroxysmal to persistent and permanent forms.
We aimed to create a molecular map of atrial fibrillation and find the distinct genetic programs underlying cell type-specific atrial remodeling and disease progression.
We used an ovine model of long-standing persistent atrial fibrillation, sampled right and left atrial tissue and isolated cardiomyocytes from control, intermediate (transition) and late (chronic) time points during progression, and performed transcriptomic and proteome profiling. We merged all layers of information into a 3-component space in which we explored the genes and proteins detected and their common patterns of expression. Our data-driven analysis points at changes to extracellular matrix, inflammation, ion channel, myofibril structure, mitochondria and chromatin as hallmarks of atrial fibrillation progression. Most important, we prove that these changes occur at early stages of the disease, but not at later ones, and that the left atrium undergoes significantly more profound changes than the right atrium. The pattern of dynamic changes in gene and protein expression correspond closely with the electrical and structural remodeling demonstrated previously in the sheep model and in humans.
Our results provide novel insight into the dynamics of molecular changes that underlie atrial fibrillation-induced atrial remodeling and that make the arrhythmia become more stable and long lasting.
Experimental Model
Atrial fibrillation was induced using a tachypacing device placed at right atria. Peacemaker implantation and pacing protocol were performed as described in
PMID: 24463369.
In fact, all the samples from this study were taken from sheep used in this previous study.
Three groups of three animals each were used for each analysis on this study: transition (11.33±4.04 days of self-sustained AF without reversal to sinus rhythm), chronic or long-standing persistent AF (365.33±10.50 days of self-sustained AF without reversal to sinus rhythm) and control group (two sham operated animals and one non operated, always in sinus rhythm).
Analysis workflow
