BMAL1-HIF2A heterodimer modulates circadian variations of myocardial injury.

ABSTRACT: Acute myocardial infarction is a leading cause of morbidity and mortality worldwide¹. Clinical studies have shown that the severity of cardiac injury after myocardial infarction exhibits a circadian pattern, with larger infarcts and poorer outcomes in patients experiencing morning-onset events^2-7. However, the molecular mechanisms underlying these diurnal variations remain unclear. Here we show that the core circadian transcription factor BMAL1^7-11 regulates circadian-dependent myocardial injury by forming a transcriptionally active heterodimer with a non-canonical partner-hypoxia-inducible factor 2 alpha (HIF2A)^12-16-in a diurnal manner. To substantiate this finding, we determined the cryo-EM structure of the BMAL1-HIF2A-DNA complex, revealing s

SUBMITTER: Ruan W 

PROVIDER: S-EPMC12095075 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature