In their new study published in Nature, scientists led by Dr. Eltzschig uncovered a molecular partnership inside the heart that makes morning heart attacks more severe. In essence, your heart has its own internal security system that’s strongest during daylight hours but weakens overnight, leaving you more vulnerable when trouble strikes before dawn.

This security system involves two key proteins with complicated names. BMAL1 is the body’s internal timekeeper. It helps regulate our daily rhythms, influencing when we feel alert or sleepy. HIF2A, on the other hand, helps cells adapt to low-oxygen conditions by promoting survival mechanisms like new blood vessel growth and boosting cell protection. These two proteins team up to protect the heart from damage, but their teamwork is strongest during the day and weakest at night.

The team found that during the daytime, BMAL1 and HIF2A work together to boost the production of a protective molecule called amphiregulin, which acts as a cellular first-aid kit, helping heart cells survive and begin repairing after oxygen deprivation. When a heart attack hits during the afternoon, this natural defense system is running at full strength. But at night and early morning, BMAL1 and HIF2A levels drop, and the heart is left dangerously exposed.

The idea that heart damage could fluctuate across the day isn’t entirely new. Blood pressure, heart rate, and hormone levels all follow daily cycles. But the discovery that BMAL1, a protein best known for controlling sleep-wake rhythms, physically reshapes itself to work with a hypoxia fighter like HIF2A, gives a molecular explanation for why timing matters so much.

Using mice, the researchers showed that heart attacks inflicted at around 3 a.m. are much more injurious than those at 3 p.m. They also showed that if you remove either BMAL1 or HIF2A from heart cells, the natural rhythm of protection disappears. No matter what time the heart attack struck, the injuries were detrimental.

The study even captured the moment these proteins join forces, using a specialized technique called cryo-electron microscopy, which is essentially a super-powerful microscope that freezes samples to near absolute zero temperatures, allowing scientists to see molecular structures in extraordinary detail.

The team found ways to boost this protective system. A natural compound called nobiletin (found in citrus peels) boosted BMAL1 activity, while a drug called vadadustat stabilised HIF2A. Both reduced heart damage in mice but crucially, only when timed to match the heart’s natural protective rhythms. Administered at the wrong time, the drugs didn’t have the same protective effect.

“This discovery opens up new avenues for treating heart attacks by considering the timing of drug administration,” said Eltzschig. “Our findings highlight the potential to use targeted drugs toward these proteins to reduce the severity of heart attacks when administered at specific times.”

There’s even a hint that the heart’s immune response might be part of this rhythmic repair system. Some immune-related genes vary by time of day too, suggesting that timing therapies could one day mean protecting not just heart muscle, but also tuning the body’s immune defences after injury.

The next step is testing these ideas in clinical trials to see if humans can benefit from time-based treatments. It’s an idea in an emerging field of science called “chronotherapy,” designing treatments that work with our body’s natural rhythms rather than ignoring them.

With heart disease remaining the leading cause of death worldwide, these insights into the relationship between our body’s clock and heart attack severity could ultimately lead to time-optimised treatments that save lives.

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(Anirban Mahapatra is a scientist and author, most recently of the popular science book, When the Drugs Don’t Work: The Hidden Pandemic That Could End Medicine. The views expressed are personal.)