Heart attacks trigger a cascade of reactions in the body, and certain immune cells may worsen the damage by disrupting heart rhythm. A recent study reveals how a protein produced by these cells directly attacks heart muscle cells, paving the way for new therapeutic strategies to prevent fatal complications.
During a myocardial infarction, the obstruction of a coronary artery deprives part of the heart muscle of oxygen, leading to cell death. This situation triggers a massive immune response, with the arrival of neutrophils, white blood cells normally responsible for fighting infections.
Researchers at Massachusetts General Hospital discovered that these neutrophils produce a protein called RELMα, which drills holes in the membranes of cardiomyocytes, the cells responsible for heartbeats. This action disrupts their electrical function and promotes the appearance of dangerous heart rhythms.
Experiments on mouse models showed that suppressing the gene encoding RELMα significantly reduced the frequency of ventricular arrhythmias. Scientists used advanced techniques such as spatial RNA sequencing and high-resolution microscopy to observe this protein's action on isolated heart cells. They also found that the human equivalent of this gene, named RETN, was more expressed in damaged heart tissues, suggesting a similar mechanism in humans.
Ventricular arrhythmias, such as ventricular tachycardia and ventricular fibrillation, are feared complications after a heart attack. In ventricular tachycardia, the heart beats very fast but in a coordinated manner, while ventricular fibrillation causes disorganized and ineffective contractions. These disorders can lead to sudden cardiac arrest within minutes. Most occur within 48 hours of the attack, a period when immune cell infiltration into the heart is at its maximum.
This discovery opens up prospects for treatments specifically targeting the RELMα protein, to reduce the harmful effects of neutrophils without completely suppressing the immune response. Researchers plan to develop molecules capable of neutralizing this protein, first in animals and then in humans. Such an approach could complement current interventions, such as artery clearing procedures, to improve patient survival after a heart attack.