Understanding how the blood vessels in our heart cope with pressure

TRPV4 channels in the feedback control of coronary artery myogenic tone

Blood flow in muscles continually changes depending on whether we are resting or active. To cope with these changes, blood vessels must adapt to meet the demands of rest and exercise. This is especially true in the heart, where vessels are specially adapted to deal with the constant changes in blood pressure with the heart beating. Our blood vessels are able to respond to changes in blood flow largely through the actions of endothelial cells (ECs) and smooth muscle cells (SMCs) that line the blood vessel. ECs and SMCs control how blood vessels respond to blood pressures via important signalling molecules, calcium and nitric oxide (NO), in a sophisticated feedback system. Angina-like symptoms, such as tightness of chest, can be caused by dysfunctional ECs and SMCs, causing the blood vessel to over-constrict. In this project, Professor Dora and her team at the University of Oxford will investigate the proteins involved in calcium signalling and how NO is released by ECs. They will use live cell imaging of a coronary artery under low and normal pressures to determine which proteins allow calcium into the cells. These arteries will then be used to study how the proteins involved in calcium and NO signalling overlap and interact. As these tiny heart arteries malfunction very early in the development of heart and circulatory diseases, this project has the potential to identify important new drug targets to prevent heart attacks.