Manipulating local phosphodiesterase activity to improve cardiac function

We have made an exciting discovery about a group of enzymes called phosphodiesterases (PDEs) and their interaction within the contractile component of the heart muscle called the cardiac myofilament (MF). These PDEs have the ability to break down a molecule called cAMP within a small area around them, influencing the way certain proteins in the heart are modified. The effects of these PDEs are very localized, occurring within a radius of less than 100 nanometers. We have found a way to modulate the activity of these PDEs at the MF to enhance a signalling pathway involved in cardiac muscle function, leading to increased force generation in both rat and human heart cells. This effect is independent of changes in calcium levels and may have potential benefits in conditions where the heart muscle is overly sensitive to calcium or experiencing problems with relaxation. As part of our ongoing research project we are working on optimising our intervention so that it can be applied in living organisms.