- Atrial fibrillation (AFib) is an irregular heart rhythm and a type of arrhythmia for which there is currently no cure.
- Researchers compared atrial heart tissue from people with AFib to those without the condition to seek potential new treatments.
- In heart tissue from patients with AFib, researchers found an expansion of immune cells called macrophages, which contribute to tissue scarring.
- Further studies are needed to understand what this means for the development and prevention of AFib.
Atrial fibrillation (AFib) occurs when the two upper chambers of the heart (the atria) beat irregularly, what may lead them to get out of sync with the two lower chambers of the heart — the ventricules. This can reduce cardiac performance and lead to
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Understanding more about how specific cells in the atria function during AFib could help researchers develop treatment and prevention strategies for the condition.
Recently, researchers found that immune cells known as macrophages support inflammation and scarring in the atria, and that reducing macrophage activity reduces these effects.
“Atrial fibrillation, despite its relatively high prevalence and incidence in the U.S., often puzzles clinicians and researchers in regard to its causative foundations for any given case,” Dr. J. Wes Ulm, a bioinformatic scientific resource analyst, and biomedical data specialist at the National Institutes of Health, who was not involved in the study, told Medical News Today.
“This research sheds light on what may be a common spur for the pathophysiological processes that engender the condition and, just as important, opens the door to new treatments.”
— Dr. J. Wes Ulm
The corresponding study was published in Science.
For the study, the researchers first collected left atrial tissue from seven patients with AFib undergoing heart surgery and five people without the condition. They found macrophages expanded more than any other cell type among those with AFib compared to tissue from those without the condition.
The researchers next examined a mouse model of AFib to understand more about the link between macrophages and AFib. In doing so, they found that expanded macrophages supported inflammation and scarring of the atria—or fibrosis. This reduced electrical conduction between heart cells and ultimately led to AFib.
In genetic analyses, the researchers found that the SPP1 gene is overexpressed in macrophages during AFib. The SPP1 gene leads to the production of the osteopontin protein that promotes tissue scarring and inflammation and was elevated in the blood of patients with AFib.
To understand more about how SPP1 affects AFib, the researchers examined mice bred to lack the gene. Ultimately, they found that mice models of AFib lacking the SPP1 gene had reduced numbers of atrial macrophages and fewer signs of AFib.
The researchers also tested whether a drug that reduces macrophage activity could treat AFib in mice.
After four weeks of treatment, they found that reducing macrophage activity in this way reduced tissue scarring in the atria.
The researchers wrote that therapeutic strategies that target inflammatory macrophages and signals derived from macrophages, such as SPP1, might help reduce AFib when used alongside other strategies such as surgical valve repair, weight loss, and blood pressure management.
“The SPP-1 gene is a potential target for immunotherapy to help reduce rates of AFib. This would be a potential first-time indication for immunotherapy in the treatment of abnormal heart rhythms,” Dr. Christopher Varughese, board certified interventional cardiologist and assistant professor at the Donald and Barbara Zucker School of Medicine at Hofstra University, who was also not involved in the study, told MNT.
Dr. Varughese indicated, however, that before such treatments become available, further studies are also needed.
Dr. Maarten Hulsmans, assistant professor of radiology at Harvard Medical School, one of the study’s authors, told MNT that a small percentage of patients with AFib driven by genetic defects would potentially not benefit from immunomodulatory therapy’.
When asked about the study’s limitations, Dr. Ulm noted that while the findings are intriguing, the results are still preliminary. He noted that while the study found ‘remarkable’ links between macrophages, SPP1 expression, and AFib, it remains unclear how much these factors are actually involved in the development of the condition.
Dr. Ulm noted that the research highlights how chronic inflammation and the factors that worsen it—such as stress— may underlie a significant number of hospital visits.
“In fact, chronic inflammation is such a widespread aggravator of human disease that it’s become recognized as being a foundational source for much of the spiraling of U.S. medical costs in recent years,” he added.
“Clinicians and scientists have long suspected that the relatively high stress, poor diet, inadequate rest, and low exercise levels linked to the U.S. lifestyle may be responsible for a great deal of American morbidity and mortality, but few suspected just how significant these factors might be,” he explained.
No ‘magic bullet’ drugs without lifestyle changes
In light of this, he noted that while anti-inflammatory and anti-fibrotic drugs may help reduce AFib frequency and severity, they won’t be ‘magic bullets’.
This, he said, is because the American lifestyle and work culture may be more toxic than previously thought, ‘channeling their noxious effects in part through the pathological vehicle of chronic inflammation.’
“If the stress-fueled chronic inflammatory state is indeed as damaging to tissue and organ function as these findings indicate, then the clear implication is that the constant ‘hustle work culture’ very rapidly crashes into the wall of diminishing returns, resulting in a sicker and generally less healthy workforce that saps American health, productivity, and general community well-being,” he concluded.