LICAMM Orai1 SNPs and Peripheral Arterial Disease severity using CT angiography imaging features

Summary

Orai1 is a highly selective calcium permeable ion channel which is expressed in vascular smooth muscle cells (VSMCs), the main cellular component of the vessel wall. It is already established as an important driver of pathological vascular remodelling in cardiovascular diseases and a potential novel therapeutic target (1). We have previously shown that inhibition of Orai1 protects the heart from adverse remodelling in the context of pressure overload (2).

Peripheral arterial disease (PAD) describes atherosclerosis in the peripheral (typically leg) arteries. It presents as pain on walking (claudication) and in severe cases, chronic limb threatening ischaemia with a high risk of limb loss without emergency surgery. Most patients are claudicants and their main risk is of adverse cardiovascular events such as heart attack and stroke.

Using UK Biobank we have identified a mutant of Orai1 that is associated with peripheral arterial disease, generalized atherosclerosis and lipid metabolism. In this study we will genotype patients with PAD for this Orai1 small nucleotide polymorphism (SNP) and use their CT angiographic images to investigate if the presence of this SNP affects disease severity (plaque burden, extent of disease, classification of plaque). There will be the opportunity to delve into the images using artificial intelligence neural networks to reveal additional data.

References

1. Shawer H, Norman K, Cheng CW, Foster R, Beech DJ, Bailey MA. ORAI1 Ca 2+ Channel as a Therapeutic Target in Pathological Vascular Remodelling. Front Cell Dev Biol. 2021 Apr 6;9:653812. doi: 10.3389/fcell.2021.653812.
2. Bartoli F, Bailey MA, Rode B, Mateo P, Antigny F, Bedouet K, Gerbaud P, Gosain R, Plante J, Norman K, Gomez S, Lefebvre F, Rucker-Martin C, Ainscough JFX, Kearney MT, Bruns AF, Shi J, Appleby HL, Young RS, Shawer HM, Debant M, Gomez AM, Beech DJ, Foster R, Benitah JP, Sabourin J. Orai1 Channel Inhibition Preserves Left Ventricular Systolic Function and Normal Ca2+ Handling After Pressure Overload. Circulation. 2020 Jan 21;141(3):199-216. doi: 10.1161/CIRCULATIONAHA.118.038891.

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject area is desirable but not essential.

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