European and North American scientists to explore biology of heart failure

A collaborative network of European and North American scientists, including from the University of North Carolina at Chapel Hill School of Medicine, have been awarded a total of $6 million over five years to explore the biology of heart failure and to find new therapies for it.

The grant was awarded by Fondation Leducq Transatlantic Networks of Excellence Program, headquartered in Paris, France. Fondation Leducq is a French non-profit health research foundation, which is designed to promote collaborative research involving centers in North America and Europe in the areas of cardiovascular and neurovascular disease.

"Proteotoxicity: an unappreciated mechanism of heart disease and its potential for novel therapeutics" is the title of this network's award-winning project. "Proteotoxicity" refers to potential health consequences due to the failure of cells to degrade and clear intracellular aggregated proteins. This may include misshapen or misfolded proteins that could, for instance, disrupt intracellular messages and impede chemical reactions.

"Recent discoveries suggest that the failure to clear aggregated proteins is a major factor in hereditary and acquired cardiac and skeletal muscle diseases," said Network of Excellence Core member, Cam Patterson, MD, MBA, Ernest and Hazel Craige Distinguished Professor of Medicine and cardiology division chief at UNC. "This network is the first to harness the synergy between skeletal and cardiac muscle research in the emerging area of cardiac protein turnover and proteotoxicity by including experts in both fields."

The project's 3 main research aims are to (1) define the role of proteotoxicity in clinically relevant models of heart failure, (2) determine the networks of genes and gene products operating in cardiac muscle cell protein degradation and aggregation, (3) explore novel interventions to reduce and/or block proteotoxicity in animal models of cardiomyopathy and heart failure.