The orphan nuclear receptor Rev-erbalpha: a transcriptional link between circadian rhythmicity and cardiometabolic disease

This review focuses on recent advances on the role of the orphan nuclear receptor Rev-erbalpha, a transcription factor participating in the control of circadian rhythm and cardiometabolic disease.

Circadian patterns of cardiovascular vulnerability are well documented, with a peak incidence of cardiovascular events in the morning. Recent studies have outlined the importance of the Clock genes in the development of metabolic disorders predisposing to atherosclerosis. Rev-erbalpha is a nuclear receptor that regulates hepatic and adipose lipid metabolism as well as vascular inflammation. Moreover, Rev-erbalpha is also part of the clock transcription machinery and the target of some clock transcription factors.

These findings identify Rev-erbalpha as a modulator of cardiovascular risk factors and as a determinant of the circadian regulation of metabolic pathways. Moreover, Rev-erbalpha crosstalks with other nuclear receptors which influence atherosclerosis susceptibility. Rev-erbalpha may thus serve to integrate metabolic and circadian signals.