Abstract 9817: Shift Work Disrupts Circadian Rhythm and Mitochondrial Quality Control in the Heart

Abstract

Listen

Translate article

Circadian mis-alignment is a disturbance in the normal 24-hour light/dark cycle that regulates physiological processes in all living organisms. Mis-alignment of the circadian, such as seen in shift workers, is associated with increased risk of ischemic heart disease and worsened outcomes following myocardial infarction. However, the mechanisms by which circadian disruption leads to cardiovascular disease, is still in its infancy. In this study, we show that short-term shift work leads to loss of critical cellular quality control mechanisms from impaired autophagy gene expression. When subjected to cardiac ischemia, shift work mice exhibit greater cardiac injury and ventricular dysfunction, compared with non-shift work control mice. Cardiac dysfunction coincided with morphological defects to mitochondria and accumulation of cellular debris from impaired autophagy. Notably, shift work mice subjected to an exercise protocol prior to ischemia, had restored autophagy gene expression, resulting in a concomitant increase in autophagic flux. Restoring autophagy rescued cardiac dysfunction and attenuated morphological and structural impairments to mitochondria. Interestingly, however, exercise failed to rescue autophagy gene expression and protect against cardiac dysfunction in Clock d19 mice which are genetically deficient for Clock gene activity. These findings demonstrate that the cardioprotective effects of exercise are in part related to improved cellular quality control mechanisms that increase autophagy. Our data provide the first direct evidence that circadian mis- alignment exacerbates cardiac injury in shift work models from impaired autophagy quality control mechanisms.