Discovery could prevent stents failing in heart disease patients

Heart stent failures could be prevented thanks to a discovery by scientists at Heriot-Watt University.

Thousands of people across the UK have stents permanently inserted to expand their arteries and to keep blood flowing, treating the underlying cause of coronary heart disease (CHD).

However, approximately 5% of patients suffer damage and inflammation to the artery walls, leading to failure of the stent and annual readmittance to hospital.

Dr Stephen Yarwood, a biochemist from Heriot-Watt’s Institute of Biological Chemistry, Biophysics and Bioengineering, has identified a molecule to tackle the inflammation.

The research, funded by the British Heart Foundation (BHF) and the Scottish University Life Science Association (SULSA), should help towards reducing the number of stents rejected by patients’ bodies and the associated costs to the NHS.

Dr Yarwood said: “Our mission is to find new formulations for stents that make inflammation, and failure of the stent, much less likely.

“We knew that an enzyme called EPAC1, which sits in the cells of blood vessels, turns off inflammatory signals, like a molecular switch.

“We tested thousands of chemicals that had potential as good starting points for drug discovery projects but with no currently-known use. We found that a molecule called I942 can regulate EPAC1’s activity.

“Now we know that this molecule can prevent or reduce inflammation, our next task is to make it more effective by modifying its structure.

“It’s like a key – we know it fits in the lock, now we have to change its shape so that we can unlock the door.”

Dr Yarwood used the facilities at the European Screening Centre, Newhouse, to test thousands of chemicals to find out whether any of them could target EPAC1.

Head of biology at the European Screening Centre Dr Stuart McElroy said: “This collaboration combined Dr Yarwood’s knowledge of EPAC1’s  biology with our experience of using drug discovery to develop new tools for drug research.

“We used BioAscent’s Compound Cloud chemical library and its unique robotic capabilities to perform a smart screen of a subset of only 5,000 chemicals. We then analysed the chemical structures of promising candidates to cherry pick similar molecules from the full library to identify I942. This is a great example of the power of BioAscent’s technology.”

James Cant, BHF Scotland director, added: “Since the BHF was established, the number of people dying from coronary heart disease in Scotland has more than halved.

“However CHD is still Scotland’s single biggest killer. It claims the lives of over 6,700 people every year and there are an estimated 240,000 people in Scotland living with CHD.

“Our pioneering research into stents and new treatments for CHD has achieved a great deal but we want to do more. That’s why we are funding important projects like this by Dr Stephen Yarwood and his team at Heriot-Watt University to help improve techniques and develop new procedures for the future.”

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