Corticosteroids and circadian rhythms in the cardiovascular system

The mineralocorticoid receptor (MR) plays a central role in cardiac physiological function and disease and is thus an attractive therapeutic target for patients with heart failure. However, the incidence of significant side effects from mineralocorticoid receptor antagonist (MRA) treatment has led to investigation of new mechanisms that may enhance MR targeted therapies. Recent studies have identified the circadian clock as a novel, reciprocal interacting partner of the MR in the heart. While the closely related glucocorticoid receptor (GR) and its ligand, cortisol (corticosterone in rodents), are established regulators of the circadian clock, new data suggest that the MR can also regulate circadian clock gene expression and timing. This review will discuss the role of the MR and its ligands in the regulation of the circadian clock in the heart and the implications of dysregulation of these systems for cardiac disease progression, and for MR activation.