Heart attacks remain one of the leading causes of death worldwide, but not all heart attacks are the same.
Doctors have long noticed something puzzling: the time of day when a heart attack happens can change how severe it is.
Heart attacks in the morning are often more dangerous and more likely to lead to death compared to those that happen later in the day.
Until recently, nobody fully understood why. A new study from UTHealth Houston may finally provide the answer, and the results could lead to better treatments that take the body’s natural rhythms into account.
To understand this research, it helps to know a little about how the body works. Our bodies run on a circadian rhythm—an internal clock that controls when we sleep, wake up, and how our organs function during the day and night. This rhythm is guided by certain proteins. One of these proteins is called BMAL1.
It plays a key role in controlling biological processes, including sleep cycles, metabolism, and hormone release. Another important protein, HIF2A, helps the body respond to low oxygen levels, something that happens during a heart attack when blood flow to the heart is blocked.
HIF2A stimulates the production of red blood cells, encourages the growth of new blood vessels, and helps cells survive when oxygen is scarce.
The researchers discovered that BMAL1 and HIF2A interact in a way that changes how the heart responds to low oxygen depending on the time of day. This interaction influences the severity of heart damage. For example, when a heart attack happens around 3 a.m., the damage tends to be greater.
The heart muscle has a harder time adjusting to the sudden loss of oxygen, which leads to larger injury and a higher risk of heart failure. In contrast, heart attacks that happen in the afternoon, around 3 p.m., tend to cause less damage. At this time of day, the heart seems better prepared to adapt, heal, and recover.
The researchers also found that these two proteins affect a gene called amphiregulin (AREG). This gene plays an important role in determining how much damage the heart suffers throughout the day.
When scientists experimented with drugs that targeted the BMAL1-HIF2A-AREG pathway, they discovered they could protect the heart—especially if the drugs were given at the right time of day.
This suggests that future treatments for heart attack patients could be more effective if doctors consider the body’s internal clock when deciding when to give certain medications. It could also apply to people undergoing heart surgery, where timing and oxygen supply are critical factors.
One example is the drug vadadustat, which activates the hypoxia-inducible factor pathway. Researchers believe that giving such drugs at carefully chosen times might reduce the risk of serious complications from surgery or heart attacks. This idea—known as chronotherapy—focuses on timing treatments to match the body’s natural rhythms.
The research team used advanced tools such as cryo-electron microscopy to study the exact structure of how BMAL1 and HIF2A interact. This gave them the first direct molecular evidence that these proteins form a complex, offering new opportunities to design drugs that target them.
The study was led by Dr. Holger Eltzschig and colleagues at McGovern Medical School, with contributions from Dr. Wei Ruan, Dr. Kuang-Lei Tsai, and Dr. Tao Li.
These findings are important for both patients and doctors. For patients, it highlights the importance of seeking help immediately if symptoms of a heart attack appear, no matter the time of day.
For doctors, it suggests that understanding the body’s natural clock could help save lives by improving treatment strategies. Heart disease is still the number one killer in many countries, and even small improvements in how treatments are given could make a big difference.
Reviewing the study findings, the discovery that BMAL1 and HIF2A work together to influence heart attack severity is groundbreaking. It explains why the same event—a blocked artery—can have worse outcomes in the morning than in the afternoon.
By revealing the role of AREG in this process, researchers have also provided a target for new drugs. The next step will be clinical trials to test whether giving these drugs at specific times can truly improve survival and recovery in patients. If successful, this approach could change the way we treat heart attacks and surgeries forever.
If you care about heart health, please read studies about a new cause of heart rhythm disorders and eating just one cup of nitrate-rich vegetables daily can reduce heart disease risk.
For more about heart health, please read studies about blood thinners that may not prevent stroke in people with heartbeat problems and this diabetes drug may protect heart health in older veterans.
The study is published in Nature.
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