The University of Texas Health Science Center at Houston (UTHealth Houston) researchers have discovered a molecular mechanism that explains why heart attack severity can vary depending on the time of day. This insight could lead to new treatments synchronized with the circadian rhythm.
Findings from the study were published in Nature. Previous studies suggested that morning heart attacks result in more severe damage, but the reasons were not well understood.
Holger Eltzschig, MD, PhD, senior author, and chair at McGovern Medical School, said, “If you have a heart attack in the morning, you are more likely to have fatal arrhythmias, heart failure, and you’re more likely to die from it. The question we asked is ‘Why?’”
In their study, researchers identified that the interaction between proteins BMAL1 and HIF2A is crucial to the time-of-day differences in heart injury severity. BMAL1 is involved in sleep-wake cycles and other processes, while HIF2A helps the body adapt to low oxygen levels by stimulating red blood cell production, promoting blood vessel growth, and enhancing cell survival.
Researchers noted that heart attacks at different times affected the heart's response to injury. Morning heart attacks led to greater damage, while afternoon attacks were less severe, allowing better adaptation and healing.
The study found that proteins BMAL1 and HIF2A affect a gene called amphiregulin (AREG), which regulates heart damage extent. Aligning drug treatments with circadian phases showed promise in offering protection to the heart.
Eltzschig stated, “This discovery opens up new avenues for treating heart attacks by considering the timing of drug administration.” He added that targeted drugs might reduce the severity of heart attacks when given at specific times, which could also benefit patients undergoing cardiac surgery.
The research team, including Kuang-Lei Tsai, PhD, and Tao Li, PhD, used cryo-electron microscopy to reveal structural interactions between BMAL1 and HIF2A, aiding future drug development.
Wei Ruan, MD, PhD, was the first author. Other UTHealth Houston contributors include multiple experts across various disciplines, along with researchers from Yale University, Harvard Medical School, Shenzhen Bay Laboratory, and Johns Hopkins Medicine.
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