What does aspirin do to you?
Acetylsalicylic acid, most commonly known as aspirin, was already part of the Egyptian pharmacopeia, used also in ancient Greece and in the Middle Ages to break fevers. Taken all over the world to kill pain and reduce inflammation, today aspirin helps to prevent heart attacks, strokes and blood clots. Its emerging role in preventing and treating cancer is on the rise too. But how does this drug act on your blood cells? ERC grantee Prof Valerie O’Donnell works on the answer.
Prof. O'Donnell and her team study lipids. These molecules play a key role in regulating blood clotting, signalling during infections and providing energy during metabolism. O'Donnell is among the first to take a close look at the total number and diversity of lipids present in platelets, blood cells that are essential for clotting.
"Most scientists working in the field focus their attention on lipids that are already identified and known. Our approach has been to try and discover how many lipids a human cell contains and to discover new ones that could be important for clotting. To do so, we spent several years setting up complicated technology and informatics," says O'Donnell.
The research team filtered and cleaned a huge data set obtained through analysing platelet lipids, finding more than 5,600 in the cells. They also worked out how the lipids differ when platelets are activated to clot, or when donors take low dose aspirin "When the platelets are activated to clot – for instance during bleeding - they make over 700 lipids. We found that aspirin blocks the generation of half of those, and these are precisely the ones we are going after. By decoding their structures, we can begin to study their potential role in promoting cardiovascular diseases and cancer metastasis," explains the ERC grantee.
Prof. O’Donnell also observed differences in response to aspirin from one donor to another. “Our objective is now to measure these differences across a larger sample of individuals, but also to measure the variation of responses, for the same person over time. For the moment, we have no idea if one's reaction to aspirin remains stable in the longer term," says O’Donnell.
By profiling thousands of new lipids, the study provides a new resource for other biomedical researchers that it is hoped will lead to discovery of new molecules involved in clotting, both in health and disease. The ERC-funded project also found many new oxidized lipids and revealed how platelets, when activated for coagulation, use membrane lipids as their main source of energy. The key findings have just been published in Cell Metabolism.
With EU funding and the support of Welcome Trust and British Heart Foundation, Prof. O’Donnell has set up an interdisciplinary team of researchers at the Systems Immunity Research Institute (Cardiff University, UK). Her group tackle new questions and ideas about the key role of lipid metabolism during inflammation and vascular disease.
O'Donnell: “Without ERC funding, this project would simply have not been possible”.
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