Pinpointing the proteins that promote atherosclerosis

Unravelling the mechanisms of apolipoprotein and serum amyloid A aggregation in atherosclerosis (Miss Abigail Wright)

Deposits of amyloid protein are probably better known for being involved in neurodegenerative disorders such as Alzheimer’s disease. But there is increasing evidence that these amyloid ‘plaques’ also accumulate with the fatty deposits that fur up the lining of arteries. The main culprit is a protein called apolipoprotein A-I, which can collect together with amyloid to form plaques. Research suggests that inflammation of the vessel wall increases the deposit of this protein and the subsequent build-up of atherosclerotic plaques Expanding on this discovery, this studentship supervised by Professor David Middleton, aims to investigate whether this mechanism holds true for other types of apolipoprotein – and for another protein called serum amyloid A. The student will study the aggregation of different proteins under controlled, identical pro-inflammatory conditions, and then will test the toxicity of the proteins to human heart blood vessel cells. This will help determine whether it is the effects of these hardened deposits or the loss of beneficial free apolipoprotein A-I that harms blood vessel cells. The final stage will be to test whether natural substances such as polyphenols and curcumin can inhibit these toxic effects, and could have potential to prevent and treat atherosclerosis.