01:25pm Saturday 19 August 2017

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 and paracrine signalling’ by Paolo Madeddu et al in Scientific Reports [open access]

Further information

The study was supported by a grant from Heart Research UK, with additional contribution from the Medical Research Council (MRC), British Heart Foundation (BHF), and the Biomedical Research Unit in Cardiovascular Disease, National Institute Health Research (NIHR) Biomedical Research Unit (BRU). The Bristol Heart Institute is part of the BHF Centre of Excellence in Vascular Regeneration.

About Heart Research UK
Heart Research UK is a visionary charity that has been helping hearts near you since 1967.  It funds ground-breaking medical research that benefits patients as soon as possible.  Over the last 50 years the charity has funded over £24 m on medical research in hospitals and universities across the UK as well as £1.7m on innovative community-based lifestyle projects that help people live healthier, happier and longer lives.  Unique, for a national charity, we spend money where it is given, helping hearts near you.

About Bristol Heart Institute
Bristol Heart Institute is one of seven newly created Specialist Research Institutes (SRIs) designed to reflect Bristol’s strength and depth in key specialisms.

The institute is a world-leading centre for translational cardiovascular research and the leading academic cardiac surgery centre in the UK. Specialising in preventing, predicting, detecting, reducing and treating cardiovascular disease, it brings together scientists and clinicians from across the University and the NHS in Bristol; training the next generation of cardiovascular scientists and clinical academics.


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