Broken Heart?

Plenty more fish in the sea
One in three deaths in the UK occur as a result of heart and circulatory diseases and, for the moment, there’s no cure for a […]

Art by Inez Januszczak

One in three deaths in the UK occur as a result of heart and circulatory diseases and, for the moment, there’s no cure for a broken heart. When our hearts are damaged, the muscle is unable to recover, however this is not true for the humble zebrafish.

A member of the minnow family, the zebrafish is not only a popular pet but is also proving to be a useful research guide, showing us how to repair damaged heart muscle. These tropical fish are able to repair their hearts, even when up to 20% has been damaged or removed. Researchers both in the UK and abroad are now working on ways to reproduce this phenomenon in human hearts.

Until recently it was thought that future treatments for heart damage would involve stem cells. These cells have the unique ability to replenish their own numbers and mature into other cell types. Hence it was thought that their transplantation directly into damaged hearts could help the heart to repair. However, research from the Centre of Regenerative Medicine in Barcelona shows that zebrafish use adult heart tissue rather than stem cells to repair their hearts.

Izpisúa Belmonte and his team in Barcelona used the transparency of the zebrafish to their advantage. Using microscopes they were able to look at the hearts of living fish, watch them beating, and see the blood flow around their bodies. They also observed damaged hearts heal in real time, and while watching this process they saw something unexpected and quite miraculous.

First, a blood clot formed over the heart wound. This happened almost immediately to prevent death due to loss of blood. The outer membrane of the heart, known as the epicardium, then enveloped the damaged area and began to stimulate repair. The epicardium appeared to signal to the adult heart cells close to the wounded area. These adult heart cells changed shape, pulled away from their neighbours and began to divide, replacing damaged tissue.

It was previously thought that as heart muscle cells are highly specialised functional cells, they would not be able to function in repair. Indeed, during our evolution, these same cells in human hearts seem to have lost their ability to respond to damage in this way. It is hoped that if we have a better understanding of how zebrafish heart cells sense and respond to heart damage, we may be able to coax our own heart cells into a more stem cell-like state, allowing them to multiply and repair damaged heart tissue just like the zebrafish. Promisingly, this research has already shown some encouraging results.

Thymosine beta-4, a zebrafish protein with a human equivalent, is to be the focus of a new heart-repairing drug. Research by Professor Paul Riley from the Institute of Child Health, University College London, has shown that this protein is involved in controlling the epicardial membrane so that it triggers new heart growth and angiogenesis (the growth of blood vessels into the damaged area). The aim of the research is to develop a drug treatment to increase the levels of Thymosine beta-4 in the epicardium and so encourage repair. Just imagine, in the future mending a broken heart may be as routine as fixing a broken leg! “If we could find a biological way of repairing damaged cardiac muscle, it would certainly obviate the need for heart transplants for some people who have had heart attacks,” says Professor Peter Weissberg, medical director of the British Heart Foundation (BHF). The BHF have acknowledged the promise of this research and have recently announced an extra fifty million pounds to be made available over the next five years to develop the field of regenerative medicine.

Advances in medical treatments has, over the last few decades, resulted in a fall in the number of deaths from heart attacks. However, an ageing population and the very fact that more people are surviving heart attacks has resulted in over 750,000 people living in the UK with the burden of heart damage. It is amazing to think that a tiny fish could hold the promise of a better quality of life for so many, and with the spawning of a new approach to healing hearts, it would seem that this research is no red herring.

About Stuart Meiklejohn

Stuart Meiklejohn is a DPhil student studying zebrafish development at the Weatherall Institute of Molecular Medicine.