It could be in the genes

Heart disease claims thousands of lives every year in the Republic with deaths caused by heart attack and stroke

Heart disease claims thousands of lives every year in the Republic with deaths caused by heart attack and stroke. Scientists at NUI Galway hope to fight back against this heavy toll using a powerful genetic technology, gene therapy.

Gene therapy involves the transfer of genetic material into cells in an attempt to replace or correct the malfunction of a specific gene. It either stops a mutant gene from producing a faulty protein or inserts an extra gene that boosts protein production.

Its application in the area of heart disease is lead by Dr Afshin Samali, research director of the cell stress and apoptosis research group within the university's biochemistry department and the National Centre for Biomedical Engineering Science.

The key to the work is understanding what happens during "apoptosis", the process of cell death, according to Dr Samali. People lose millions of cells every day through this tightly regulated process, even though they are completely unaware of it.

READ MORE

"We want to know exactly what goes on inside the cell to make it kill itself," said Dr Samali. When a cell goes "haywire" during a heart attack or in diseases, such as Parkinson's or Alzheimer's, the cells "rapidly switch on the programme for death and kill themselves. If we understand what is the molecular basis for cell death, we can manipulate it."

His seven-member research group, which takes on three more members next month, is particularly interested in the apoptosis associated with heart attack. An attack occurs when a blood clot forms in an artery feeding the heart. This stops blood flow, starving the cells of both oxygen and glucose, the fuel that cells use for energy.

Cells under this type of physical assault immediately release special substances known as heat shock proteins or stress proteins. Research has shown that these proteins help the cells survive the challenge unless conditions become so severe that apoptosis begins.

Dr Samali is using rat heart muscle cells, cardiomyocytes, in culture to study these processes. Similar cultures of human aortic smooth muscle cells are also studied for their response to lack of oxygen (hypoxia) and lack of both oxygen and glucose (ischemia).

The team detects the stress proteins released during these two conditions and have so far identified 100 proteins of interest.

"We are looking at the cell signalling during ischemia and hypoxia. We want to know the role of these proteins and what is the mechanism of their actions."

It is laborious work. The genes for each protein must be identified and isolated. The researchers use a virus "carrier" to bring a target gene into a test cell and then put it under stress to see how the protein either aids survival or brings on apoptosis.

This points the way towards novel new treatments however. Sometimes just after a heart attack, other blood vessels open allowing fresh blood to reach oxygen-starved heart muscle cells.

Instead of helping the cells to survive, the rush of fresh blood, called reperfusion, has the opposite effect, killing off the stressed cells and compounding the damage.

Something similar happens during heart, liver and kidney transplants when blood supply is restored and also following a stroke to brain tissue, said Dr Samali.

The gene therapy being developed at NUI Galway may help. While they can't block the initial heart damage, they would use a harmless virus to insert a gene and boost production inside the cells of heat shock proteins. This might aid cell survival during reperfusion after heart attack or organ transplantation, said Dr Samali.

His group will collaborate closely over the coming years with the gene therapy research programme headed by Prof Timothy O'Brien, professor of medicine at NUI Galway.

This strong clinical link will allow discoveries in the lab to be brought quickly into medical practice, Dr Samali believes.

The Wellcome Trust, Enterprise Ireland, the Irish Heart Foundation, the EU and NUI Galway all contributed to this research effort.