Developing an MRI test to predict heart attack risk in coronary heart disease patients

Molecular imaging of dysfunctional matrix remodelling in arterial disease

Patients with coronary heart disease have arteries which have been damaged by the build-up of ‘fatty plaques’ in the vessel wall, which can eventually rupture to cause a blood clot that leads to a heart attack. Some fatty plaques – a mixture of fats, white blood cells and other materials including the protein elastin – are more likely to rupture than others. In particular, those with a weaker protein ‘wall’ between the plaque and the inside of the vessel seem to be more likely to burst. But we don’t have a reliable, safe test that can tell the difference between different types of plaque in living patients. Professor Rene Botnar’s team from Kings College London, aims to develop a test to diagnose which coronary heart disease patients are most at risk, using a magnetic resonance imaging (MRI) scan. Such a test could prioritise the highest risk patients for the most intensive treatments, as well as de-prioritising low risk patients and putting their minds at rest. Thanks to a previous BHF grant, the team has found a potentially crucial difference between high- and low-risk plaques in mice. High-risk plaques have lower levels of elastin – a strong, supple substance – and instead have more ‘tropoelastin’, an elastin-like material which is not so robust. More tropoelastin in a plaque means it is more likely to become unstable and rupture. The team aims to develop a test using one of three molecules that bind to tropoelastin. They will combine these ‘tracer’ molecules with an agent that will light up in the MRI scan, signalling a plaque that’s more likely to rupture. They will also follow up another previous discovery, that a molecule called LOX seems to be malfunctioning in weaker plaques with more tropoelastin. They will attempt to reverse the lowering in LOX levels using currently available drugs in order to gain a better understanding of why some plaques are more likely to burst. As this research is still at an early stage, the researchers will need to test their techniques in mice and rabbits before moving on to patients. But the findings may lead to a test that will lead to great benefit to heart patients by telling doctors who is most at risk.