Recipient organisationNIHR Guy's and St Thomas' Clinical Research Facility
NIHR supportRecorded as supported by this research centre
PeriodFeb 2025 — Mar 2025
In plain English
AI plain-English summary
Arteries clog with fatty plaques or balloon into aneurysms, and both can kill. This project will analyse human tissue samples—plaque and aneurysm wall removed during surgery, plus blood—to find the cellular and molecular fingerprints driving these two forms of vascular disease. Current treatments for blocked arteries carry significant risks of bleeding, stroke, and death. Aneurysm surgery is expensive and also carries mortality risk. The fundamental gap is that doctors lack therapies that prevent plaques or aneurysms from forming or progressing in the first place. They also lack reliable biomarkers to track disease worsening. If this work identifies the key mechanisms behind arterial occlusion and dilatation, it could lead to drugs that stop plaque growth or aneurysm expansion before they become life-threatening. It might also yield blood tests that flag patients at highest risk, allowing earlier intervention. The research is fundamental science—it uses cell cultures and animal models alongside human samples—so no immediate clinical tool will emerge. But similar mechanistic studies of atherosclerosis have already led to statins and anti-platelet drugs. A deeper understanding of these two disease pathways could open the door to the next generation of vascular therapies.
View original technical description
Atherosclerosis is a progressive arterial disease, resulting in the development of fat-rich plaques in artery walls. Plaques that grow may block arteries, or become unstable and rupture, causing blood clots (arterial occlusive disease: AOD). Blockage with blood clot or pieces of clot (emboli) may give rise to conditions such as heart attacks, stroke and limbs with poor blood supply(limb ischaemia)that are a major cause of death and morbidity. Current medical and surgical treatments for AOD carry significant risks of bleeding, increased incidence of stroke and death. Weakening of the artery wall can also give rise to ballooning (aneurysm) that may rupture and lead to blood loss and death. Aneurysms are surgically treated, but these treatments are expensive or have significant mortality. A better understanding of the mechanisms that give rise to and propagate arterial occlusion (plaque) or arterial dilatation (aneurysms) would facilitate the development of therapies aimed at preventing plaque or aneurysm development and progression, or biomarkers of disease progression. This may come from blood samples and samples of plaque or aneurysm wall (that are available and normally disposed of during surgery) from which we can analyse the cellular and molecular ‘fingerprints’ of these conditions.The proposed work is part of an ongoing programme that uses cells in culture and animal models to examine the cellular and molecular mechanisms that give rise to disease development and progression. We will therefore request ethical approval for a 5 year project in the first instance and review a possible extension after that time. All tissues obtained will be those normally disposed of during routine surgery. Blood samples will be taken either as an extra amount during routine sampling or as a separate sample.
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