Is oxidation of the protein TAK1 an important factor in the progression of heart failure?

Studying transforming growth factor-beta-activated kinase (TAK1) thiol-dependent activation and its role in heart failure

Heart failure is a debilitating condition where the heart cannot pump blood around the body effectively. It is a leading cause of death in the UK. We need to improve our understanding of the underlying biochemistry of heart failure so we can develop effective new treatments to slow its progression and ideally prevent it altogether. One of the most common triggers for the development of heart failure is a heart attack – when blood supply to the heart muscle becomes blocked. Once the blockage is cleared and blood flow is restored, there is a burst of chemicals called ‘reactive oxygen species’ (oxidants). These oxidants are known to be involved in the heart muscle damage caused by a heart attack and subsequent inflammation. Dr Joseph Burgoyne, a BHF Research Fellow at King’s College London, has discovered that oxidants react with a protein called TAK1.This enhances the activity of TAK1 and triggers biological signals that are associated with heart damage and heart failure. Dr Burgoyne believes that blocking the oxidant-induced activation of TAK1 could prevent biological processes that lead to heart damage and the subsequent progression to heart failure. He will now test this idea by studying the hearts of genetically-engineered mice in which TAK1 cannot be activated by these oxidants. Establishing TAK1 oxidation as a new drug target could lead to the development of a new effective treatment to prevent heart failure.