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Song Receives AHA Grant to Study Contradictory Protein

Long-Sheng Song, Professor in Cardiovascular Medicine, has received a three-year, $300,000 Transformational Project Award (TPA) from the American Heart Association. This TPA will fund Dr. Song’s research into potential new targeted therapies in the prevention of heart failure development and progression. Heart failure is the most common cause of hospitalization in patients older than age 65 and new therapeutic approaches for heart failure are still critically needed.

Dr. Song and his colleagues have focused on the cellular failure that results from impaired cardiac excitation-contraction (EC) coupling, the process that triggers a myocyte, or heart muscle cell, to contract and relax. One key component of this coupling is the myocyte transverse-tubule (TT) system. When myocytes begin to fail, human and animal models have shown, the TT system undergoes disruptive remodeling with a cascade of complications. By better understanding the mechanisms behind this remodeling in different types of heart disease, Dr. Song hopes to identify ways to restore or repair the TT system and thus improve cardiac function.

The funds from the TPA will fuel research into a potential target in a muscle-specific protein called Mitsugumin 53 (MG53), which has been detected at increased levels in failing human hearts and animal models of chronic heart failure but is also involved in membrane repair after acute injury. Initial data from the Song lab showed that overexpression of MG53 protected against TT damage, although long-term overexpression resulted in severe disruption. “These seemingly opposite data,” Dr. Song said, “led to the hypothesis that MG53-mediated membrane repair is necessary in the short term to protect against T-tubule damage in response to cardiac stress, whereas chronic long-term upregulation of MG53 leads to myocyte TT membrane damage and EC coupling dysfunction instead of membrane repair.” Dr. Song will test this hypothesis in both human and mouse models of the TT membrane structure, which is a previously unstudied area, as he and his lab search for new heart failure treatments to promote repair while avoiding side effects.