Analysing immune samples from diseased aortic valves, to understand what causes T-cell accumulation and inflammation in aortic stenosis patients, to identify new treatment targets for the condition.
Aetiology
The aortic valve controls the blood flow between the left ventricle of the heart, and the aorta – the body’s largest blood vessel. The opening of this valve allows blood to be pumped to the rest of the body, and its closing prevents the backflow of blood into the heart. Aortic stenosis (AS) is a narrowing of the aortic valve, caused by thickening and stiffening of the aortic valve. In patients with AS, the narrowing of the valve limits how much blood can reach the rest of the body, which places strain on the heart, which can lead to heart failure if left untreated. AS is one of the most common heart conditions, affecting around 300,000 people over the age of 55 in the UK, and causing more than 100,000 deaths globally each year.
Currently, there are no medicines that can stop or slow down this process, and the only treatment option is surgery to replace the valve once the damage has become irreversible. However, this surgery is not suitable for all patients and carries its own risks, including the replacement valve also failing. Therefore, there is a critical need to develop a new way to prevent or delay the progression of the disease before surgery is required.
This has led Dr Francesca Bartoli-Leonard at the University of Bristol to develop a new approach to studying the immune system of those with AS, to gain insight into better understand how to treat the disease. T cells are a type of immune cell the body uses to defend against infection and disease. In AS patients, T cells frequently build-up inside the diseased valve, leading to inflammation which restricts the function of the valve. It is unknown what causes the T cells to build-up here, so the researchers will collect samples from diseased aortic valves removed during surgery and analyse the T cells from them to understand what is causing them to gather there and drive disease.
This research aims to explore how the immune system damages the valve, which could help identify early-stage treatment options. Through understanding which specific immune system signals cause inflammation in the aortic valve, treatments aimed at blocking these signals may slow down the disease’s progression. This has the potential to reduce the need for major heart surgery in AS patients, improving their quality of life and treatment outcomes.
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