British Heart Foundation-funded project can shine light on causes of heart attacks and strokes
Scientists at Manchester Metropolitan University will develop a new way of studying the formation of dangerous blood clots after winning funding for the work.
Dr Sarah Jones, Senior Lecturer at the University's School of Healthcare Science, will focus specifically on developing a new experimental model to study the causes of heart attacks and strokes.
They are two of the most common cardiovascular conditions which collectively are the leading cause of death globally and responsible for more than one in four deaths in the UK.
The project is being made possible thanks to a grant from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) and the British Heart Foundation (BHF).
Heart attacks and strokes commonly arise when important blood vessels in the body become clogged with a fatty substance known as atherosclerotic plaque. This can cause the arteries to harden and narrow.
Disruption of these plaques can trigger the formation of a blood clot, blocking up the artery and starving the tissue of oxygen and nutrients. This process is called 'atherothrombosis'.
In previous projects looking at blood clots in arteries, researchers have focused on looking at the blood vessels of animals such as mice and rats, however there are significant differences between how the condition presents in different species.
Dr Jones and her team at Manchester Metropolitan will attempt to develop a model in the laboratory which more accurately represents this disease in humans.
It involves coating a tiny channel on a chip with the proteins found in the blood vessel wall and growing cells which line blood vessels on top of these proteins.
Human blood will then be passed through the channel to replicate how a blood vessel works.
The researchers will then intentionally damage the cells to recreate a blood clot to observe the process and allow new drugs, which prevent heart attacks and strokes, to be tested.
Dr Jones said: “The trigger for blood clot formation is damage to the blood vessel wall, caused when fatty plaques break open, or the surface of the blood vessel wall detaches, exposing blood to the ‘sticky’ proteins, which lie beneath.
“This study will develop materials to recreate these sticky surfaces, and will be covered by endothelial cells - the cells that line the blood vessels.
“We will then damage the endothelial cells to trigger blood clot formation simulating atherothrombosis.
“This will enable us to improve our understanding of how blood clots that cause heart attacks and strokes develop, as well as testing out new drugs to treat patients.
“The model will use human blood, human endothelial cells and will take into account forces such as blood flow and heart rate that are found in human coronary arteries.
“This should mean that the model is much more relevant, and will allow us to more accurately investigate how blood clots form in patients having a heart attack.
“This approach is not only important in terms of giving us the best method with which to understand the clots and what causes them, but also in relation to efforts that are going on across the sector to reduce and refine the use of animals in cardiovascular research.”
This project will enable us to improve our understanding of how blood clots that cause heart attacks and strokes develop, as well as testing out new drugs to treat patients
BHF Senior Research Advisor Noel Faherty said: “We are pleased to be supporting this project which will create a more accurate and meaningful way of investigating the cause of dangerous blood clots in the arteries. We hope this work will lead to the development of anti-thrombotic drugs which are more effective and more targeted to patients’ needs.
“At the BHF we ensure we only fund animal research when absolutely necessary and we actively encourage our funded researchers to plan their studies so fewer animals are needed and to look for other possible research methods. This study is a great example of researchers looking beyond animal models to improve their methodology and to generate stronger scientific results.”
The NC3Rs and BHF have provided a £90,000 grant to fund the project, which is a three year PhD studentship.