Cardiologists have observed for decades that heart attacks are more damaging when they occur during the day than at night, and understanding why that happens may be the key to treating the condition, a new study finds.
There are many theories as to why daytime heart attacks are more harmful. Some suggest that stress hormones and daily fluctuations in blood pressure may be to blame. However, the role of the immune system is still unclear.
you may like
The damage increases day by day
Analyzing the clinical records of more than 2,000 heart attack patients, the research team found that patients admitted during the day had higher neutrophil counts and greater heart damage, suggesting that neutrophils themselves may be involved in worsening the damage. Later, experiments using mice confirmed the same pattern.
The researchers divided the laboratory mice into two groups. One had normal neutrophil levels, and the other had reduced neutrophil levels with antibody treatment. They then induced heart attacks in the mice at different times of the day and night.
In the first set of mice, we observed a pronounced rhythm in which heart damage was greater in the morning than at night, similar to what was seen in the human data. However, in mice with low neutrophil counts, this rhythm disappeared, reducing the overall damage caused by a heart attack.
To further test this idea, the researchers genetically disabled a gene that helps control the circadian clock, a regulator of the body’s 24-hour cycle. As they expected, these engineered mice lost the rhythm again and had less overall heart damage.
Importantly, the scientists found that although depletion of neutrophils hinders the immune system, deleting just the clock gene does not impair the mice’s ability to fight infections.
“This makes this study very interesting,” Tim Ramerman, an immunologist at the University of Münster in Germany who was not involved in the study, told Live Science. That’s because it was always believed that immune defense and neutrophil-mediated inflammatory damage were “inseparable from each other.”
you may like
Put neutrophils into “night mode”
The scientists then wanted to test whether there was another way to control this gene and mimic the body’s natural nighttime neutrophil sedation without reducing the number of cells. They focused on a receptor on neutrophils called CXCR4. This receptor normally responds to signals that slow down neutrophil activity at night.
They genetically engineered mice to have very high concentrations of this receptor. This allowed the cells to calm down even during the day, reducing the damage to the heart again and causing the rhythm pattern to disappear.
Finally, using a drug that activated this receptor, the researchers reduced neutrophil activity during the day and pushed the cells into a nighttime state. Researchers have found that treatment with the drug before a heart attack reduces tissue damage and improves heart function weeks after the attack.
Additionally, in a mouse model of sickle cell disease, where neutrophils clog blood vessels and cause severe inflammation, the drug reduced blood vessel blockage and improved blood flow.
It was surprising that regulating just one type of immune cell provided significant protection against these inflammatory insults, Andres Hidalgo, the study’s senior author and an immunologist at Yale University, told Live Science.
Dr. Lammerman noted that experiments with this drug were particularly important because they provided evidence that the compound reduces the inflammatory response of neutrophils while keeping their defense mechanisms intact.
The researchers also uncovered an interesting pattern behind the actions of neutrophils. In skin wounds and heart tissue alike, neutrophils during the day tend to spread to adjacent intact areas and enlarge the injured area, Hidalgo explained. On the other hand, milder nocturnal neutrophils remain trapped in the center of the injury zone.
The findings suggest there may be a way to fine-tune neutrophils to make them less aggressive without compromising their defensive abilities. However, applying this approach to humans requires careful research. How CXCR4 signaling affects other cell types also needs to be carefully considered, Lammermann cautioned.
A drug that suppresses inflammation without compromising immunity will be the holy grail of immunotherapy. But he added that human trials of such drugs would need to evaluate many factors, including when they should be given in the event of a heart attack and whether there are any potential risks.
This article is for informational purposes only and does not provide medical advice.
Source link
