Professor Ajay Shah
BHF Chair of
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.
Read more about our past heart failure