Time of Day Impacts Heart Attack Severity: New Research Reveals Why & points to Potential Treatments
HOUSTON,TX – Researchers at UTHealth Houston have identified a molecular mechanism explaining why heart attacks are frequently enough more severe when they occur in the morning. Published in Nature, the study reveals a critical interaction between two proteins, BMAL1 and HIF2A, that influences the heart’s response to oxygen deprivation during a heart attack, and suggests a path towards timing treatments to maximize effectiveness.
Previous studies have consistently shown that morning heart attacks lead to greater heart damage, higher rates of complications like arrhythmias and heart failure, and increased mortality. This new research pinpoints why.
“We knew the time of day mattered, but the underlying reason remained a mystery,” explains Dr.Holger Eltzschig, senior author and chair of the department of Anesthesiology, Critical Care and Pain Medicine at McGovern Medical School at UTHealth Houston. “Our work shows that the interplay between BMAL1 – a key regulator of the body’s circadian rhythm – and HIF2A – a protein that helps cells adapt to low oxygen – significantly impacts how heart cells respond to the stress of a heart attack.”
The study, conducted on mice, demonstrated that heart attacks occurring around 3 a.m. resulted in more extensive damage compared to those at 3 p.m.This difference was linked to the BMAL1 and HIF2A proteins and their influence on a gene called amphiregulin (AREG), which plays a crucial role in heart damage repair.
Importantly, researchers found that by targeting the BMAL1-HIF2A-AREG pathway with drugs, they could protect the heart, particularly when treatment was timed to coincide with the body’s natural circadian rhythm.
“This discovery opens up exciting possibilities for improving heart attack treatment,” says Dr. Eltzschig.”By considering the body’s internal clock,we might potentially be able to administer drugs at optimal times to reduce damage. This could also benefit patients undergoing cardiac surgery.” He specifically mentions drugs like vadadustat, a hypoxia-inducible factor activator, as potential candidates for timed management.
the research team utilized advanced cryo-electron microscopy to visualize the detailed interaction between BMAL1 and HIF2A, providing a foundation for future drug growth.Future clinical trials are planned to determine if aligning treatment with the body’s circadian rhythm can improve patient outcomes.
Key Researchers: wei Ruan,MD,PhD; Kuang-Lei Tsai,PhD; Tao Li,PhD; and Holger Eltzschig,MD,PhD.
