New discovery could reverse tissue damage caused by heart attacks

A new discovery by University of
Bristol scientists helps to explain how cells which surround blood vessels,
called pericytes, stimulate new blood vessels to grow with the hormone ‘leptin’
playing a key role. Leptin is produced by fat cells which helps to regulate
energy balance in the body by inhibiting the appetite. This study,
described in Scientific
Reports, may have important implications for the treatment of heart
attacks and also for cancer, the two main killers in the UK.

The growth of new blood vessels,
called ‘angiogenesis’, is an important process occurring both in health and
disease. It is involved in the repair of tissues following injury but also has
an essential role in the growth and spread of cancer.

The Heart Research UK-funded project studied how pericytes encourage the growth of
new blood vessels and the role of leptin, and provides important new
information about the mechanisms involved.

One of the current treatments for
heart attack is coronary artery bypass surgery. This uses blood vessels from
the leg, or elsewhere in the body, to bypass the blocked artery and improve
blood flow to the heart muscle. This is invasive and major surgery, with a long
recovery time. In the longer term, these findings may help in the development
of an alternative treatment to major surgery for heart attack patients.

Importantly, the team found
that pericytes produced 40-times more leptin when exposed to low levels of
oxygen and that this continued until oxygen levels returned to normal. This may
help tissues to build more blood vessels to increase blood flow and oxygen
supply. Together with other findings, the research shows that leptin has
several important actions which encourage new blood vessel growth in areas
where tissues are deprived of oxygen.

In most cases, a heart attack is
when a coronary artery becomes blocked and the resulting lack of blood supply
to the heart muscle can lead to a damaged heart. Professor Madeddu’s team
has shown that by stimulating the growth of new blood vessels, pericytes have
the potential to restore blood supply to damaged heart muscle after a heart
attack.

Paolo Madeddu, Professor of Experimental Cardiovascular Medicine from the School of Clinical Sciences, who leads the project at the Bristol Heart Institute, said:

“This new discovery could have important implications
for the treatment of heart attacks, which is when a main coronary artery gets
blocked, but also cancer. These results reveal a new signalling mechanism
that may have a far-reaching and significant impact on cardiovascular
regenerative medicine.

“Increasing leptin in
pericytes in a damaged heart might help it to heal faster, whereas blocking the
production of leptin in cancerous pericytes might starve the tumour of
nutrients and force it to shrink.”

Barbara Harpham, Chief Executive
of Heart Research UK, added:

“This translational research project is a good
example of research that aims to benefit patients as soon as possible.
Professor Madeddu and the team have made some important new discoveries. Understanding
more about the processes involved may help pave the way for the development of
new treatments for heart attacks which could replace coronary bypass
operations.”

Paper: ‘The adipokine leptin modulates adventitial pericyte functions by autocrine andparacrine signalling’ by Paolo Madeddu et al in Scientific Reports