Circadian Clock Key to Heart Attack Severity

In a recent interview, Holger Eltzschig, MD, PhD, of McGovern Medical School at UTHealth Houston, discussed groundbreaking research on circadian variation in myocardial injury, revealing why heart attacks that occur in the early morning tend to be more severe than those in the afternoon. Dr. Eltzschig’s team identified BMAL1, a core circadian transcription factor, as a key regulator in this phenomenon, forming an unexpected complex with HIF2-Alpha, a hypoxia-inducible factor, to drive amphiregulin expression—a cardioprotective molecule. Through a combination of human cardiac biopsy studies, mouse heart attack models, in vitro hypoxia experiments, and structural analysis via cryo-electron microscopy, the researchers demonstrated how this BMAL1-HIF2-Alpha complex mitigates myocardial damage by preventing myocyte apoptosis. Deleting any of these components abolished the time-of-day differences in infarct severity, while pharmacologic activation of this pathway showed promise for perioperative protection.