Ajay Shah

Professor Ajay Shah

BHF Professor of Cardiology

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



Heart attack and heart failure

Lorraine had a heart attack in 2005 and has since been diagnosed with heart failure, a debilitating condition for which there is no cure. Her children, Charlotte and James, have had to grow up fast. 

Blood vessels and heart disease

The lining inside blood vessels plays a vital role in maintaining a healthy circulatory system because it prevents a build up of fatty deposits called atherosclerosis. Problems with the blood vessel lining, called endothelial dysfunction, can lead to heart disease and heart attacks, which can ultimately result in heart failure like Lorraine's.

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

BHF Professor Ajay 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 how these enzymes are involved endothelial dysfunction. The research will hopefully lead to new agents to prevent endothelial dysfunction, and 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 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 they may be able to promote protective signals and prevent harmful signals. They are researching new ways to tip the balance of these signals to prevent and treat heart failure.

Professor Shah's research could offer new hope to people like Lorraine and her family. But we need your help to continue funding live saving research. 

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