White blood cells that respond to heart attacks are more active during the day. Bringing them back to a night mode protects the heart from overreacting.
Clinical experience says that heart attacks in the early morning are more dangerous than those that occur at night. A study published in Journal of Experimental Medicine (JEM) could now explain why: neutrophils, the white blood cells that intervene – even with counterproductive effects – in case of tissue damage, are more active and inclined to cause excessive inflammation during the day. Forcing them to act as if they were in “night mode” appears to protect the heart-stricken heart from collateral tissue damage.
Our defenses follow circadian rhythms
Since humans are diurnal animals, our defense system is more active during the day, when we are more likely to come into contact with a pathogen. But some immune players, such as neutrophilic white blood cells, are also on the front line in cases of acute inflammation: during a heart attack, surgery, a burn, trauma. However, their attempt to promote inflammatory mechanisms and replace damaged cells can go beyond what is necessary and end up damaging healthy tissue as well.
Almost half of the damage to the heart after a heart attack is due to inflammation caused by neutrophil activity: the extent of the damage, however, fluctuates throughout the day, a fact that suggests that neutrophil activity is also subject to circadian rhythms, the internal physiological cycles that regulate all the functions of our body.
Heart attacks: the night alleviates them
A collaboration of scientists coordinated by Yale University and the Spanish National Center for Cardiovascular Research analyzed data from thousands of patients in a Spanish hospital to confirm that, due to reduced neutrophil activity, nocturnal heart attacks cause less serious damage to heart tissue. Then, the researchers confirmed that in mice, as in humans, heart attacks in the early hours of the morning cause more extensive damage to the heart, precisely because of the increased activity of neutrophils at this time of day.
At this point the team verified that there is a strategy to “block” the biological clock of neutrophils and freeze it in nocturnal mode: this trick makes it possible to limit tissue damage in the event of a myocardial infarction, because at night the white blood cells seem to intervene only where it is actually necessary, in the center of the initial wound, and not in the surrounding areas where there are healthy tissues. At night, in practice, their action is more targeted and less massive and random.
The drug is a molecule called ATI2341 that mimics a compound naturally produced by our bodies at night: It targets a receptor on the surface of neutrophils and changes the cellular behavior of white blood cells, putting them into a less active mode.
Less inflamed but still protected
In this way it is possible to regulate inflammation without compromising the immune defenses. According to the study authors, blocking the circadian rhythms of neutrophils not only protected the hearts of mice, but improved the response to certain pathogens and reduced other harmful inflammatory processes. The findings could pave the way for new therapies to protect internal organs from damage caused by excessive inflammation.
