The National Institutes of Health has awarded an Oklahoma Medical Research Foundation scientist $3.1 million to investigate a possible cause of heart disease among people with diabetes.
Chi Fung Lee, Ph.D., will use the five-year grant to better understand how obesity and diabetes contribute to cardiomyopathy, which is an abnormal weakening of the heart muscle.
Lee’s lab studies the mechanisms that contribute to heart disease. One particular focus is a molecule called NAD+, which is crucial for generating energy. Previous studies have shown a connection between diminishing levels of NAD+ and cardiomyopathy.
People with diabetes are far more likely than others to develop cardiomyopathy and other types of heart disease, Lee said. He attributes that to diminishing levels of NAD+.
“NAD+ is part of the electrical wiring of our metabolism,” said Lee, who came to OMRF from the University of Washington in 2019. “When that wiring is compromised in the heart, it reduces the heart’s ability to pump blood to the whole body, ultimately leading to heart failure.”
With this grant, his lab will focus on the role of an enzyme called SARM1. Scientists have studied it for years for its role in killing nerve fibers that carry impulses away from the brain. Lee’s team is the first to look at its role in the heart.
“Our early research indicates that this enzyme drives the decline of NAD+ in the hearts of people with diabetes and obesity and contributes to the progression of heart disease,” Lee said.
The research could give way to new and better treatments for heart disease.
“Most research involving this enzyme has focused on the brain,” said scientist Lijun Xia, M.D., Ph.D., who leads OMRF’s Cardiovascular Biology Research Program. “Clinical trials have tested a drug to inhibit it to treat neurological disorders. If his hypothesis proves correct, it could lead to new testing of that drug to treat heart disease.”
Lee’s grant (No. 1R01HL164854-01A1) was funded by the National Heart, Lung, and Blood Institute, a part of the NIH. Funding for Lee’s preliminary data was provided by Oklahoma City’s Presbyterian Health Foundation and the Oklahoma Center for Adult Stem Cell Research. Additional funding was provided by a Centers of Biomedical Research Excellence grant from the National Institute of General Medical Sciences, also a part of the NIH.
