University of Alabama at Birmingham have been awarded a four-year, $2.3 million grant from the National Heart, Lung and Blood Institute to study macrophage circadian rhythms in heart failure.Researchers at the
Sumanth Prabhu, M.D., director of the Division of Cardiovascular Disease, and Martin Young, D.Phil., professor in the Division of Cardiovascular Disease, will serve as principal investigators.
According to Prabhu and Young, one of the key components in terms of discovery is that heart failure, a very common disease, is well recognized as a state of inappropriate inflammation.
“However, we don’t really know why there is so much persistence of inflammation,” Prabhu said, “and we have been unable, to date, to use anti-inflammatory therapies for therapeutic benefit for heart failure — clinical trials using different approaches have failed thus far.”
He added that their team is proposing a novel idea that disrupted circadian clocks in the macrophages themselves underlie the inflammation and subsequent progression of heart failure.
Prabhu and Young will have three specific aims during the four-year study:
- To delineate those alterations in the macrophage circadian clock in heart failure that promote inflammation and left ventricular remodeling
- To define the role of the clock-controlled immune activator E4BP4 in inflammation and remodeling in heart failure
- To establish the potential of targeting the circadian clock as an immunomodulatory therapy in heart failure
“This represents a completely different way to immunomodulate the heart failure state,” Prabhu said. “So, the project has significant implications, both scientifically for our understanding of disease and for heart failure therapeutics that specifically target inflammation.”
Young added that the findings will fill present knowledge gaps and uncover new mechanisms underlying circadian biology, immune cell function and cardiac remodeling and identify a novel approach to correcting the molecular clock in heart failure.