A Dublin research group has discovered a 'switch' that controls blood clotting, a finding that could help reduce the risk of heart attacks and strokes, writes Dick Ahlstrom.
An Irish research team has identified a key molecular "switch" involved in the formation of blood clots. The finding could help reduce the human toll claimed by one of Ireland's biggest killers, cardiovascular disease.
Abnormal blood clotting or thrombosis that blocks blood vessels can lead to heart attack and stroke. The discovery at the Royal College of Surgeons in Ireland (RCSI) of a protein switch involved in thrombosis could open up new ways to halt inappropriate clotting.
Adequate clotting is essential for good health but when platelets, the key cells involved in the process, get it wrong this can spell danger, explains RCSI senior lecturer, Niamh Moran.
"We are very interested in the role of the platelets in blood clotting," Dr Moran explains. "When they get a little bit wrong that is how you get blood clots that cause heart attacks, strokes and angina. We want to understand how platelets get involved in this and ultimately to develop drugs to help."
She supervised research carried out by PhD candidate Deirdre Larkin in the department of clinical pharmacology in association with the RCSI's centre for human proteomics. The €15 million centre is one of the major CSETs (Centre for Science, Engineering and Technology) funded by Science Foundation Ireland.
"They have this amazing array of 37,200 human proteins on a single chip. It is quite a unique resource," explains Moran. Larkin used the chip in her search for the protein switch involved in the blood clotting process.
Each platelet carries its own switch, telling it when to become "sticky" to form a clot. The switch itself is a protein with the ungainly name "integrin alpha II b beta three" , says Moran.
"The integrin is like a switch, it turns on and off. If it is off the platelet is quiet, if on the platelet is active. We wanted to know how the integrin works. Nobody knew how it is switched on and off."
The RCSI team had a clue however, a fragment of the integrin protein itself. They built a string of amino acids, a peptide, that matched the integrin fragment and then used the peptide to see if it made any connections on the protein chip.
They got two "hits" among the 37,200 proteins, two matching samples of a single protein known as ICln. "It doesn't have a cutesy name," Moran acknowledged, but ICln has emerged as a hugely significant discovery. It is the missing switch that binds to integrin to turn it on and off.
"We think the ICln doesn't like to bind with the integrin in normal circumstances, but when the platelet is activated the icln binds to the integrin," explains Moran. "It is one dimension of the control of platelets, but it is an important one."
The most significant aspect of the discovery is it now gives researchers huge potential for the development of new therapies for the treatment of cardiovascular disease. The research group has already discovered a chemical compound that can block the ICln to integrin binding, in effect halting the clotting process. It may offer a route towards a drug that can reduce the risk of unwanted clotting. It may also lead to new diagnostic tools, allowing clinicians to identify those most at risk from the disease.