Genetic discovery hope for heart attack victims
Breakthrough hailed after therapy repaired scar tissue
SCARRING in damaged hearts can be reversed by the injection of three vital genes, a groundbreaking study has shown.
The research holds out the hope of helping heart attack patients to recover better.
Scientists used a virus to carry the genes directly into the scar tissue of mice that had suffered heart attacks.
Tests showed the fibroblast cells responsible for scarring began to transform into beating heart cells.
Evidence suggests the same technique could be used to combat scarring in other parts of the body.
It might then be possible to regenerate nerve cells in patients with spinal cord injuries, and pancreatic cells in diabetics, say the scientists.
Professor Peter Weissberg, medical director at the British Heart Foundation (BHF), said moreworkwasneededtoconfirm the research but it would be a “remarkable achievement” if scarring could be reversed.
Healthy hearts consist of different kinds of cells, including beating muscle cardiomyocytes and fibroblasts that provide structural support. When a person has a heart attack, fibroblast cells migrate to the site of damage and form a scar.
“The process at first can be considered beneficial, since without fibroblasts adding structural support damaged hearts would rupture,” said study leader Dr Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Diseases in San Francisco in the USA.
“But later difficulties arise when the fibrotic scar doesn’t contract like the muscle it has replaced. Reduced global contractility means the heart has to work much harder, and the extra stress can ultimately lead to heart failure and even death.”
One of the holy grails of heart research has been to repair heart attack damage by replacing lost cardiomyocytes.
The latest work, presented at the Frontiers in Cardiovascular Biology meeting at Imperial College London, emerged from
Similar approaches, could be used to regenerate nerve cells for patients with spinal cord injuries
research on the genetic factors that drive heart development in embryos.
Dr Srivastava’s team identified three key genes – Gata4, Mef2c and Tbx5 – that were able to convert fibroblasts taken from the hearts of adult mice into cardiomyocytes.
When the genes were injected into mouse scar tissue in a laboratory dish, the fibroblasts differentiated into cardiomyocyte-like cells.
“The fibroblasts converted into cells with nice patterns of striations, typical of myocytes, and developed units that could generate f o r c e,” s a i d Dr Srivastava.
The next stage was to inject the same genes directly into the scar tissue of mice that had just suffered a heart attack. A virus was used to ferry the genes into the animals’ hearts.
“We’ve obtained even better results showing that the fibroblasts become more l i ke cardiomyocytes and functionally couple with their neighbours,” said Dr Srivastava.
“They could beat in synchrony and improve the function of the heart.”
He pointed out that major questions had to be answered before the technique could be considered as a potential heart attack treatment.
However, he added: “Fibroblasts throughout the body have the potential to be transformed, which means that similar approaches, using different factors, could be used to regenerate nerve cells for patients with spinal cord injuries, and other cells for diabetic patients.”
Professor Weissberg said: “This research illustrates one of many routes scientists are exploring to try and repair damage caused by a heart attack.”