Alterations to MLC2 in human tissue; a suspect for poor contraction in heart failure

Human cardiac myosin light chain 2: Functional impact of phosphorylation and deamidation

Over half a million people in the UK have been diagnosed with heart failure, a condition where the heart lacks the power to meet the demands of the body. It’s a progressive condition that can cause debilitating symptoms of fluid build-up and breathlessness. Current treatments delay, but do not prevent progression, and new hope is urgently needed. In heart failure, the proteins in heart muscle cells that should contract strongly to create the pumping action don’t work very well. The reasons for this are not yet well understood. Professor Pieter de Tombe and his team are studying a component of the contraction machinery called myosin light chain 2 (MLC2). In heart failure, MLC2 undergoes chemical alterations that may disrupt the ability of the heart muscle to contract properly. However, most studies of MLC2 have involved mice and there are subtle but potentially crucial differences in the protein between small animals and humans. In this project the team will investigate, for the first time in human tissue samples, the impact of heart failure-related changes to MLC2 on the ability of heart cells to contract. Deeper understanding of how human MLC2 works may pave the way towards the development of urgently needed new treatment strategies to combat heart failure.