Differential effects of REV-ERBα/β agonism on cardiac gene expression, metabolism, and contractile function in a mouse model of circadian disruption
Sobuj Mia, Mariame Selma Kane, Mary N. Latimer, Cristine J. Reitz, Ravi Sonkar, Gloria A. Benavides, S. Ray Smith, Stuart J. Frank, Tami A. Martino, Jianhua Zhang, Victor Darley‐Usmar, Martin E. Young
Abstract
Circadian clocks are composed of more than 10 interconnected transcriptional modulators, all of which have the potential to influence the cardiac transcriptome (and ultimately cardiac processes). Previous studies indicate that cardiomyocyte-specific BMAL1 knockout (CBK) mice exhibit a dysfunctional circadian clock (including decreased REV-ERBα/β expression) in the heart, associated with abnormalities in cardiac mitochondrial function, metabolism, signaling, and contractile function. Here we highlight decreased REV-ERBα/β as a mediator of glycogen synthesis, cardiomyocyte size, interstitial fibrosis, and contractile function abnormalities observed in CBK hearts.