Modulation of cardiac systolic and diastolic properties by oxidation dependant activation of protein kinase G: Is phospholamban the only regulator?
Each heartbeat consists of two phases: systole and diastole. During systole, heart muscle cells – cardiomyocytes – in the lower chambers of the heart contract (shorten) to pump blood out of the heart. During diastole, these lower chamber cardiomyocytes relax (elongate) to refill with blood ready for the next contraction. This cycle of cell shortening and elongation is achieved by the movement of calcium in and around the cardiomyocyte. A protein called protein kinase GI? (PKGI-alpha) influences calcium movement and so the function of myofilaments. Activity of PKGI-alpha is controlled by a small molecule called cGMP, or a chemical reaction called oxidation. Recently, scientists discovered that if oxidation of PKGI-alpha is blocked, many changes occur in the calcium cycle and the pumping ability of the heart is impaired. In this project, Dr Luigi Venetucci at the University of Manchester aims to assess the effects of PKGI-alpha oxidation on the function of the heart, and find out precisely how oxidised PKGI-alpha exerts these effects. To achieve this, Dr Venetucci and colleagues will study the hearts, heart muscle fibres, and cardiomyocytes of genetically-engineered mice in which PKGI-alpha cannot be activated by oxidation. This research could establish PKGI-alpha oxidation as a new drug target for treatments to improve the pumping ability of the heart in conditions like heart failure.
Project details
| Grant amount | £305,757 |
|---|---|
| Grant type | Project Grants |
| Application type | Project Grant |
| Start Date | 30 March 2020 |
| Duration | 3 years |
| Reference | PG/19/82/34760 |
| Status | In Progress |
