The role of Nrf2 (nuclear factor erythroid 2 related factor 2) in the cardiac response to chronic overload stress.

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Heart failure is a leading cause of morbidity and mortality. New treatments are required to address this growing problem. Understanding the mechanisms involved in the development of heart failure is the key to developing new treatments. When a heart is under prolonged stress, such as high blood pressure, it initially adapts to preserve its function. However, with time, its strength declines and heart failure ensues. A complex interplay between protective and damaging cellular pathways determines whether the heart adapts or fails. This project will study the role of a master regulator of genes, known as Nrf2, which we believe may play a key role in activating protective pathways in the heart. The project will study the role of Nrf2 in protecting the heart during exposure to chronic high blood pressure and will investigate the pathways activated by Nrf2 that are involved in such protection. By using state-of-the-art methodology to analyse the complex changes coordinated and regulated by Nrf2, we hope that the project will provide novel insights into key mechanisms involved in the development of heart failure and therefore lead to the identification of novel therapeutic targets for this debilitating condition.