Gene that prevents heart regeneration discovered

Scientists have discovered a gene that "could rejuvenate old hearts" according to The Daily Telegraph. The newspaper goes on to say that "damaged hearts could be regenerated simply by switching off a gene which prevents cells from dividing".

Some parts of our body, such as our skin, are made up of cells that divide and reproduce throughout our lives to produce new tissue. This is known as mitosis. Other parts, such as the heart, are thought to lose this ability shortly after birth.

The Telegraph story is based on new research in mice that has identified a specific gene – dubbed the ‘heartbreak gene’ by the Mail Online – called Meis1 that appears to block the heart tissue’s ability to regenerate.

The researchers found that using various techniques to ‘switch off’ the Meis1 gene did lead to the production of new heart cells in mice.

The hope is that similar techniques could be used in humans to repair damage to the heart that can occur in cases of heart failure.

But switching off a gene to treat a progressive disease like heart failure is unlikely to be quite as simple as the Telegraph suggests. Much more research is needed before we may see a groundbreaking new treatment capable of healing ‘broken hearts’.

Where did the story come from?

The study was carried out by researchers from the University of Texas Southwestern Medical Center in the US, Ain Shams University in Egypt and the University of Queensland in Australia. The research was funded by the American Heart Association, the Gilead Sciences Research Scholars Program in Cardiovascular Disease, the Foundation for Heart Failure research and the US National Institutes of Health.

The study was published in the peer-reviewed journal Nature.

The media reporting of this research was generally accurate, despite some confusion from Mail Online about a "rogue gene" that stops "heart cells dividing uncontrollably".

Most importantly, the media headlines should not be interpreted to mean that “revolutionary new treatments” are on the horizon. The idea of using genes to treat disease – gene therapy – has been around since the 1970s. But, currently, there is only one licensed medication on the market that makes use of gene therapy techniques.

What kind of research was this?

This was animal and laboratory research that aimed to identify and describe the process that controls the generation of new heart cells in newborns. Newborns are able to produce new heart cells to replace injured cells. However, this ability is lost early in life (generally by seven days after birth), and the adult heart lacks this regenerative capacity.

Previous research has suggested that a gene called Meis1 is involved in the development of the foetal heart, and may be involved in regulating the regeneration of newborn heart cells. The researchers thought that this gene may also play a role in the loss of this regenerative capability.

Several heart conditions lead to damage or death of heart cells and to heart failure, where the organ is unable to pump enough blood around the body.

The adult heart is not able to generate new cells to repair such injury and heart failure is considered to be a progressive disease (gets worse over time). So any technique that could reverse this progressive decline would be welcome.

But as an animal study, any results should not be assumed to apply directly to people. Significant further research is needed to determine whether the mechanisms identified in this study provide a suitable target for addressing human heart failure or other causes of heart damage.

What did the research involve?

The researchers carried out a series of experiments to define the role of Meis1 in regulating the generation of new heart cells.

They first measured expression levels of the gene to determine how these levels changed during the first seven days of life (after which the heart is no longer able to produce new cells). Gene expression is the process through which the information encoded in our genes is used to produce proteins. Measuring the level of gene expression shows how active the gene is.

They next investigated the effect on heart cell generation of removing the Meis1 gene, using both rat heart cells as well as mice models.

The mice lacking a copy of the Meis1 gene were compared to control mice (which had copies of the gene) on several factors, including:

• changes in the production of new heart cells
• characteristics of the heart cells
• the size and function of the heart

These comparisons were made for newborn as well as adult mice.

Next, the researchers increased the expression of Meis1 to determine whether doing so produced an effect on the generation of new heart cells in mice.

Finally, they carried out a series of tests to determine how the Meis1 interacted with other parts of the system to identify the mechanism by which the gene controls heart cell generation.

What were the basic results?

The researchers found that there was an increase in Meis1 expression over the course of the first week of life, and that this expression continued into adulthood.

When Meis1 was removed, the researchers found that rat heart cells were able to produce new cells. Mice lacking the Meis1 gene exhibited a similar increase in the production of new heart cells.

Fourteen days after birth (which corresponds to one week after the heart typically stops producing new cells) these mice had hearts of similar size and function to control mice that retained the Meis1 gene. The researchers found that the hearts of mice lacking the Meis1 gene had significantly more cells that those of the control mice, and that these heart cells were smaller in size compared with controls.

When investigating the effect of the Meis1 gene of the adult mouse heart, the researchers found that heart size and function were normal in these mice at both four weeks old and at seven months old. There was also no difference in the size of the heart cells.

The mice lacking the Meis1 gene continued to produce new heart cells into adulthood, but the rate at which they produced these cells slowed as they aged.

The researchers found that newborn mice engineered to overexpress Meis1 did not generate new heart cells in response to injury, while control mice hearts regenerated normally.

Finally, the study authors identified several interactions between Meis1 and other genes in the system that controls the production of new heart cells. They found that when Meis1 is deleted, there is increased activity among some genes that promote the generation of new heart cells. There was also a corresponding decrease in the activity of genes that normally inhibit the production of these new cells.

How did the researchers interpret the results?

The researchers conclude that Meis1 is a critical component of the system that regulates the production of new heart cells. They say their research suggests that cell cycle arrest in the adult human heart (whereby the heart no longer generates new cells) may, theoretically, be reversed.

Conclusion

This research identifies a possible mechanism that leads to the inability of the adult heart to repair itself. It is premature to suggest that the study heralds a new era in treating heart failure.

As with much early stage cell and animal research, this study is probably most useful for scientists and suggests future research paths that may be helpful in the quest to treat heart conditions. It is too early to tell, however, whether the Meis1 gene will prove to be a useful target for future therapies, let alone whether treatments targeting the gene or its products will be safe and effective enough for treating heart failure patients.

Current treatments for heart failure, while a lot better than they used to be, are only of limited effectiveness. So the message is still that prevention is better than cure.

Effective ways you can reduce your risk of heart failure include:

• quit smoking if you smoke
• maintain a healthy weight
• eat a healthy diet
• take plenty of exercise

Read more about heart failure.