Professor Ajay Shah

BHF Chair of Cardiology

King’s College London School of Medicine
BHF Centre of Research Excellence

Blood vessels and heart disease

The lining inside blood vessels (endothelium) plays a vital role in maintaining a healthy circulatory system because it has properties that prevents a build up of fatty deposits (atherosclerosis). Problems with the blood vessel lining (endothelial dysfunction) can lead to heart disease.

A major cause of endothelial dysfunction is excess production of chemicals called reactive oxygen species (ROS) which destroy beneficial molecules produced by the endothelium. ROS also make the lining 'sticky' so that circulating blood cells attach to it and migrate into the vessel wall – the first stages of atherosclerosis.

Professor Shah and his team have identified a new group of enzymes called NADPH oxidases as major sources of ROS in the blood vessel lining. The team is now working to define the regulation of these enzymes and their role in the development of endothelial dysfunction. It is hoped that the research will lead to new agents to prevent endothelial dysfunction, and therefore protect blood vessels.

Signals leading to heart failure

A healthy heart is able to adapt to increased workload through changes in its structure and function. For example, a long-distance runner can train their heart to work harder than normal. This type of adaption is regulated by specific signals generated within cells in the heart. The signals promote changes in the activity of new genes, and the production of new proteins.

A damaged heart - for example, after a heart attack - has a higher workload and adapts to this situation. However, in the long-term, the changes are detrimental and can cause the development of heart failure. It is thought that heart failure results because of an imbalance between beneficial (or protective) signals and detrimental signals.

Professor Shah’s team have discovered that different NADPH oxidase enzymes control beneficial and detrimental signals that are generated during the adaptation of the diseased heart. They are currently working to define the effect these enzymes have on a heart facing an increased workload.

The team believe it may be feasible to promote protective signals and prevent harmful signals. They are researching new ways to tip the balance of signals in search of better ways to prevent and treat heart failure.

Further information