New Study Reveals How Circadian Rhythms Influence Heart Attack Severity at the Molecular Level

Recent research conducted by scientists at the University of Texas Health Science Center at Houston has uncovered the molecular mechanisms explaining why the severity of heart attacks can vary depending on the time of day. Published in the journal Nature, this groundbreaking study highlights the role of circadian rhythm proteins in regulating cardiac response to injury.

The study focused on the interaction between two key proteins: BMAL1, a core circadian clock component, and HIF2A, a protein vital for cell survival under low oxygen conditions. Researchers found that these proteins form a heterodimer—an important complex—that influences the heart’s ability to cope with ischemic injury (lack of blood flow). The interaction between BMAL1 and HIF2A affects the expression of the gene amphiregulin (AREG), which plays a crucial role in reducing heart damage.

Interestingly, the timing of a heart attack significantly influences its impact. The study revealed that attacks occurring around 3 a.m., the body's biological night, result in larger infarcts and greater risk of heart failure, compared to those happening in the afternoon. This variation is regulated by molecular changes in the BMAL1–HIF2A complex, which is more effective during certain circadian phases.

Using advanced cryo-electron microscopy, the researchers mapped the detailed structural interactions between these proteins, providing insights that could guide the development of new targeted therapies. By possibly modulating the BMAL1–HIF2A pathway, future treatments may be timed to align with the body's circadian rhythms, enhancing their effectiveness.

The findings suggest that administering drugs to activate or inhibit these proteins at specific times could minimize heart damage during a myocardial infarction. For example, drugs like the hypoxia-inducible factor activator vadadustat might offer better protection if given before surgery or during high-risk periods.

Lead researcher Dr. Holger Eltzschig emphasized the future potential: "Our discovery opens the door for chronotherapy in cardiology, where treatment timing is optimized to match the body's internal clock. Further clinical studies are necessary to explore this promising approach."

This research not only deepens our understanding of the molecular basis of heart attack variability but also paves the way for improving patient outcomes through precise timing of therapeutic interventions.