Grant: Project Grant

Circadian rhythms are 24 hour cycles that regulate physical, mental, and behavioral changes in our body. There is increasing evidence in recent years showing that circadian rhythms play a critical role in the pathogenesis of heart attacks. This is best exemplified by the observation that disrupted circadian rhythm, such as seen in shift workers, dramatically increases the chance for heart attack and heart failure (HF), compared with non-shift workers. However, the underlying mechanism for the severity of heart attack in response to disrupted circadian remains poorly understood. Our exciting preliminary studies suggest that disrupted circadian rhythm results in abnormal lipid metabolism and accumulation of lipids in the heart from dysregulation of circadian gene expression, and may be the underlying cause of HF following heart attack. Furthermore, we show that the loss of circadian regulation predisposes the heart to increased injury following heart attack from disrupted clearance of accumulated lipids. For this reason, the overarching goal of this proposal is to determine how circadian genes affect lipid metabolism following heart attack and to understand how modulation of circadian proteins can improve lipid metabolism and cardiac function following heart attack. Since shift work is extremely common in modern world, accounting for 30% of the working population and disruption of the normal light/dark cycles exacerbates adverse cardiac outcomes, increases infarct size and leads to cardiac dysfunction following heart attack, it is highly important to understand the mechanisms that underlie the connection between circadian rhythm and lipid metabolism following heart attack, toward the long-term goal of developing new therapies to treat HF.