Researchers from Baylor College of Medicine and the University of Oxford have identified a molecular mechanism that, when targeted, helped reduce heart tissue scarring and lower the frequency of heart rhythm disturbances in mice.
The findings, published in the journal Nature Cardiovascular Research, point to a potential new approach to treating atrial fibrillation, a condition for which existing therapies cannot directly reverse structural changes in the heart.
Atrial fibrillation is the most common type of heart rhythm disorder. In this condition, the upper chambers of the heart beat irregularly. It increases the risk of ischemic stroke, heart failure and myocardial infarction, and may also be associated with a higher likelihood of developing dementia and kidney disease. According to the researchers, the condition affects more than 10 million adults in the United States.
One complication of atrial fibrillation is atrial fibrosis, the formation of scar tissue that alters the structure of the heart muscle and contributes to further rhythm disturbances. Current treatments can help control heart rate, but there are no therapies specifically designed to reverse this process.
The scientists focused on the molecule microRNA miR-31-5p, which regulates gene activity within cells. Its levels are elevated in atrial fibroblasts — cells involved in forming and maintaining tissue structure — in patients with atrial fibrillation. This molecule reduces the production of CTR protein, which helps regulate fibroblast activity. When levels of this protein fall, the cells can become overactive and contribute to scar tissue formation.
To interrupt this process, the researchers developed a molecular blocker that prevents miR-31-5p from interfering with the regulatory mechanism controlling CTR. Experiments using human cells obtained from patients with atrial fibrillation, as well as mouse models, showed that the intervention helped restore protein levels.
In mice, the treatment not only prevented fibrosis from developing but also reduced existing scar tissue. The extent of fibrosis decreased by approximately 30% from baseline, while it continued to progress in the untreated control group. The duration and overall burden of abnormal heart rhythm episodes also decreased.
According to study co-author Xander Verheule, a professor at Baylor College of Medicine, the researchers had expected a positive effect but were surprised that the intervention was able to reverse some of the damage that had already occurred. He emphasized that further research is needed before the approach can be evaluated for use in humans.
The authors believe that targeting the identified molecular mechanism could provide the basis for future approaches to preventing and treating atrial fibrosis.
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