How do heart cells protect themselves in low oxygen environments?

Coronary microvasculature and hypoxia tolerance

Dr Ross Breckenridge and his team at University College London are studying how heart muscle cells cope in low oxygen environments and avoid damage from heart disease. During pregnancy, the heart of the developing baby adapts so it can function in the relatively low oxygen environment of the womb. But soon after birth the heart loses this ability and adult heart muscle cells are vulnerable to damage by low oxygen levels. Dr Breckenridge believes that the foetal heart has adapted to low oxygen levels by having fewer capillaries (small blood vessels that supply the heart muscle). This sparser blood supply protects the heart muscle from exposure to dangerous molecules (ROS) that can develop in low oxygen environments. Dr Breckenridge has found that a signalling pathway involving a protein called hypoxia inducible factor, or HIF, reduces the number of foetal capillaries and may protect the heart from low oxygen. In this project, Dr Breckenridge will investigate whether altering capillary density in adult mouse hearts could help heart muscle cells cope with low levels of oxygen. He will examine how capillary density changes in low oxygen levels and find out if it is possible to protect adult hearts from low oxygen using a drug that prevents capillary damage. Dr Breckenridge and his team will also study heart muscle biopsies from people with failing and recovering hearts. This will allow them to find out if there is a relationship between capillary density and protection against low levels of oxygen in people. By revealing how heart cells adapt to low oxygen in heart failure or conditions where the heart is starved of oxygen, this research could reveal clues for new treatments.