The Circadian Clock Influences Heart Performance

Circadian clocks are believed to provide the selective advantage of anticipation, thus allowing organisms to respond efficiently to stimuli at the appropriate moment. Disrupted circadian rhythms have been found to affect a variety of basic physiological processes. However, the importance of the circadian clock in regulating heart performance remains undetermined. We hypothesized that the circadian clock plays a crucial role in heart performance through the anticipation of daily workload. Echocardiography was employed to monitor heart function and structure in mice in a noninvasive, real-time manner. In wild-type mice, both the ejection fraction (EF) and the shortening fraction (FS), two important markers of cardiac function, show diurnal variation. In addition, the amplitude of the EF and the FS enlarges in response to forced exercise in a time-dependent manner. The diurnal variations in EF and FS are altered in mice with disruptions in circadian clock genes and are significantly attenuated under an imposed light regimen. Furthermore, it shows that the overexpression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Pgc1 alpha) under control of the muscle creatine kinase (MCK) promoter inhibited clock gene expression in the heart and muscle and decreased the expression of peroxisome proliferator-activated receptor alpha (Ppar alpha), metabolic genes glucose transporter (Glut4), and acetyl-coA synthetase (Acs1). Pgc1 alpha overexpression abolished the diurnal variation of EF. We thus propose that PGC1 alpha might play an important role in circadian-mediated, impaired cardiac function by regulating the circadian rhythm of metabolic genes.