Researchers at UTHealth Houston have uncovered why heart attacks that happen in the morning are often more dangerous than those that occur later in the day.
The discovery may help create new treatments that are timed to work with the body’s internal clock, also known as the circadian rhythm.
It has long been known that people who suffer heart attacks in the morning tend to have more severe heart damage and worse outcomes. These patients are more likely to experience fatal heart rhythms, heart failure, and even death. Until now, doctors didn’t fully understand why this happens.
Dr. Holger Eltzschig and his team wanted to find the cause behind this pattern. They studied the roles of two proteins in the body: BMAL1 and HIF2A. BMAL1 is a protein that helps control the body’s circadian rhythm, which influences sleep, hormone release, and metabolism.
HIF2A is a protein that helps the body survive low oxygen levels, which is important when blood flow to the heart is blocked during a heart attack.
Using mice in a preclinical study, the researchers discovered that these two proteins work together to regulate how the heart responds to a lack of oxygen. They also found that these proteins control another important gene called amphiregulin, or AREG, which plays a major role in how much damage the heart suffers during a heart attack.
The time of day had a big impact on heart damage. Heart attacks that occurred around 3 a.m. caused more harm to the heart than those that happened around 3 p.m.
The afternoon heart attacks resulted in smaller areas of damage, and the heart was better at healing itself. The researchers believe this is because of how BMAL1 and HIF2A act during different parts of the day.
When these proteins were targeted with certain drugs, the researchers were able to protect the heart from damage. They found that giving these drugs at specific times of day—when the body’s internal clock is at a certain phase—offered even better protection.
Dr. Eltzschig says this could lead to new ways of treating heart attacks. Instead of giving medicine at any time, doctors might get better results by timing the treatment to match the body’s circadian rhythm.
This idea could also help people who are having heart surgery. For example, a drug called vadadustat, which activates HIF proteins, might work better if it’s given before the operation at the right time of day.
The research team included scientists who used advanced tools like cryo-electron microscopy to look closely at how BMAL1 and HIF2A interact.
This detailed work helped confirm how the proteins work together and how they affect heart healing. These new insights could guide drug developers in designing treatments that work with the body’s natural rhythms.
In summary, this study helps explain why the time of day matters during a heart attack. By understanding the role of circadian proteins like BMAL1 and HIF2A, scientists can explore new treatment strategies that could reduce heart damage and save lives. It’s an exciting step toward personalized heart care based on our body’s own clock.
The study is published in Nature.
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