A new project uncovering genetic changes linked to damage following a heart attack could potentially pave the way for gene therapies to prevent long-term cell damage.
Dr. Mairi Brittan, a research fellow at the University of Edinburgh’s Centre for Cardiovascular Science, is the lead researcher on a project uncovering genetic changes linked to damage following a heart attack. The research could potentially pave the way for gene therapies to prevent long-term cell damage.
With funding from the British Heart Foundation, Dr. Brittan has been working to understand how regenerative cells, called endothelial progenitor cells (EPCs), can be used to treat heart and circulatory diseases. Endothelial cells that line blood vessels can become damaged in certain cardiovascular events and diseases, and EPCs have the potential to repair those damaged blood vessels and build new ones. Through previous research, Dr. Brittan discovered that EPCs might originate in the adult blood vessel wall, and she is currently working toward new strategies to identify and define the cells and understand how they behave in diseases.
When someone experiences a heart attack, millions of cells instantly die. Cells continue to die after the cardiovascular event, causing a massive spread of damage which can lead to heart failure. By using the removed hearts of patients who received a transplant after experiencing a heart attack, Dr. Brittan and her team were able to pinpoint the genes that were expressed in damaged blood vessels and heart cells. The results of the study were published in 2019 as a comprehensive atlas of gene targets that influence the process of blood vessel regeneration.
“We can essentially map the gene expression of a human patient’s heart attack, which has never been possible before,” said Dr. Brittan in an interview with The Daily Mail.
By studying gene targets, researchers can identify genes that are switched on after a heart attack. These turned-on genes could be progenitors of damage that lead to long-term consequences, and they are good targets for therapeutics to prevent such consequences. Dr. Brittan believes that gene therapies that switch off these genes could be injected soon after a heart attack, leading to improved outcomes in patients. The therapy could also stimulate genes that promote blood vessels and heart cells to repair themselves after a heart attack.
“Several other species, like the zebrafish, can repair their own heart muscle, and we want to replicate this in humans. We want to target genes and promote more successful repair that would, in turn, salvage the damaged areas of heart muscle. We would want to look at [a gene therapy] that would travel to the blood vessels and the heart. So if you introduce it, it would promote the blood vessel growth and regeneration,” she said.
The work is ongoing, and Dr. Brittan stated that the team is hoping to move towards clinical studies to begin investigating the therapy in patients.
Dr. Brittan’s work follows several other attempts to develop gene therapy for patients who have suffered from heart failure. In July 2021, researchers at the Cardiomyocyte Renewal Lab at the Texas Heart Institute began testing a gene therapy targeting the Hippo signaling pathway in pig hearts to see if the gene therapy could help injured hearts recover. The research, which stemmed from the lab of Dr. James Martin, director of the Cardiomyocyte Renewal Laboratory, was based on previous findings that when patients experience heart failure, there is an increase in the activity of the Hippo signaling pathway which inhibits heart repair.
In mice studies, turning off the pathway in mice with heart failure led to the recovery of pumping function. The therapy was then studied in pigs, who share similarities with human patients when it comes to cardiovascular events. The therapy returned positive results, showing that treated pigs had improved heart functioning and that new blood vessels have formed, making researchers hopeful that the therapy would be pushed closer to clinical trials in humans.
