Better stents for the future

Dr Janet Chamberlain

Carbon monoxide could reduce complications from stent insertions in people who have had an angioplasty procedure. Sarah Kidner talks to Dr Janet Chamberlain, who is leading the research at Sheffield University.

Every year, thousands of people in the UK receive one or more stents to improve blood flow through a narrowed segment of coronary artery called a stenosis. Stenting involves inserting a small mesh tube to widen narrowed coronary arteries. The procedure generally reduces the symptoms of coronary heart disease (CHD) and patients recover well.

However, scar tissue in the stented area can lead to the re-narrowing of the blood vessel. BHF-funded researchers believe that carbon monoxide-releasing molecules (CORMs) may help to prevent this scarring or ‘restenosis’, as Dr Janet Chamberlain, who is leading the team at Sheffield University, explains.

Why is your research important?

BHF funding figureThe most common treatment for symptomatic atherosclerosis (the underlying cause of CHD) is to put in a stent. This is a metal cage that opens up the artery and keeps it open. Unfortunately, the process of inserting the stent causes damage to the artery wall.

This causes a wound-healing reaction, creating a scar. Sometimes that scar re-blocks the artery, so instead of being blocked by the disease of atherosclerosis, the artery is blocked by a scar.

We call this re-blocking restenosis. It happens in about five per cent of patients with a stent, which doesn’t sound like a lot, but it is several thousand people a year when you consider the number of stents inserted annually.

What is the focus of this project?

Currently, we use drug-eluting stents – polymer- coated stents that release drugs – in blocked arteries, but they’re not perfect.

Other researchers have shown that CORMs can reduce the risk of inflammation, and we want to see whether they can reduce the risk of restenosis in stenting.

The focus of this study is to establish the best type of CORM to use and to find out how they are working.

Isn’t carbon monoxide toxic?

We want to see whether the carbon monoxide-releasing molecules can reduce the risk of restenosis in stenting

The body produces carbon monoxide naturally. Previously, we thought it was just a by-product that we get rid of by breathing it out, but people now recognise that it has a positive biological effect in the body.

Some have tried to increase this positive effect by giving more carbon monoxide to the body by administering it as an inhalable gas, but this comes with a lot of hazards, because too much can lead to poisoning.

The CORMs we’re working with are synthesised molecules. We’re using carbon monoxide bound to a chemical compound in the chemistry lab that releases carbon monoxide in the body, but the compound only releases it in areas where conditions are right to allow the carbon monoxide to detach.

Therefore, what happens is that the carbon monoxide is released in the body in the area where you want it, as opposed to it being breathed into the lungs, where it can cause negative side effects.

Will the stents be coated in carbon monoxide?

We’re using two different types of CORM. One releases carbon monoxide very quickly; the other releases it at a slower rate. Once we know the best one to use, we will hopefully, in a project leading on from this, look into whether we can put this on to a stent.

When might we see a clinical trial?

This project is two years long. Once we have got the results, we would be looking at another grant of two to three years in length, which would involve putting CORM on a stent and testing it in an appropriate animal model of coronary disease to ensure it is safe (see box below). If all goes well, then we would be looking into the early stages of clinical trials, but that is several years down the line.

Methods of research

The BHF is dedicated to saving lives by developing better treatments and cures for heart conditions. As part of this, we fund essential research using cells grown in a laboratory, computer models and human volunteers. Where these are not feasible, we support research involving animals.

All our grant applications go through a strict peer-review system. This ensures BHF-funded scientists follow a clear set of principles – ‘the three Rs’. We:

  • replace with non-animal alternatives whenever possible
  • reduce number of animals used
  • refine care to achieve the highest animal welfare standards. If our researchers do work with animals, their research is carried out in line with strict Home Office guidelines.

Read more about our policies on animal research.

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