Could fat in your bloodstream cause blood clots?
BHF research is shedding more light on how fats in your blood could affect your health. Dr Alan Stewart explains his research to Sarah Brealey.
You might have noticed zinc in on the label of a bottle of multivitamins. It’s also found in foods including seafood, beef, and beans.
Your body doesn’t need much zinc, but just a little is needed for almost all of its processes, including fighting infections, making new cells, and healing wounds.
Now BHF-funded research is looking at the role it might play in causing harmful blood clots. Blood clots are involved in many types of heart and circulatory disease, including the most common type of stroke, and deep vein thrombosis. Blood clots happen as a result of several different processes. Thanks to Dr Alan Stewart’s research at the University of St Andrews, we’re starting to understand how zinc is involved. What’s more, he’s finding out how the availability of zinc is affected by the fats in your blood. This could lead to potential new treatments.
Dr Stewart, who specialises in biochemistry, says: “We're looking at how zinc is transported in the body. Zinc is an important mineral that has many different functions. After we eat food that contains zinc, it's absorbed by the gut and goes into the circulation. Zinc needs to get to all parts of the body so how it's transported is quite important.”
A puzzle of proteins
Usually, zinc is carried in the blood by binding to a protein called albumin, which is the most common protein in the blood. The proteins in your body are a bit like very complicated Lego. They interact with other molecules that bind to them. Each type of protein will only bind to specific molecules, and those molecules have to fit into specific places on the protein. These interactions can change the shape of the protein and how it works. Back in 2003, Dr Stewart’s team discovered the site on the albumin molecule where zinc slots in.
Zinc needs to get to all parts of the body so how it's transported is quite important
He says: “So we knew where it happened, but that was about all. Then about two years ago, together with Prof Wladek Minor’s group at the University of Virginia, we finally managed to structurally confirm how zinc binds to albumin. This work was in part supported by BHF funding. What we managed to discover is that in the presence of fatty acids, albumin is less likely to bind to zinc. There's a particular fatty acid site which is very close to the zinc site. If a fatty acid molecule binds to that site, it changes the shape of the site and stops the zinc binding.”
There’s more than one place on the albumin molecule where fatty acids can bind. But if you have higher levels of fatty acids in your blood, it’s more likely that the site which affects zinc will be occupied by a fatty acid – meaning that zinc can’t bind to albumin and be carried along in the blood stream in the normal way.
An illustration of an albumin molecule with 5 fatty acid molecules bound.
(From coordinates in the RCSB protein databank, pdb code: 1BJ5)
Should we change our diet?
The type of foods you eat can affect the level of fatty acids in your blood. There’s already lots of evidence that obesity damages your health in many ways, but Dr Stewart says it’s too early to make specific dietary recommendations on the basis of this research.
“I don't think we can say that if you eat a particular fatty meal it will make a difference; it is more that we already know that if you have diabetes or are you will have high levels of fatty acids in the blood, and therefore this might be an issue. Cancer and fatty liver disease also cause high levels of fatty acids in the blood.”
Zinc and blood clotting
So what does this have to do with blood clots? Zinc is an important part of the clotting process. It signals to platelets which are key to blood clotting, and increases the risk of blood clotting.
Dr Stewart says: “What we suggest is if people have higher level of fatty acids in their blood, the zinc which should be bound to the albumin instead is released and may act on the clotting process.”
“Although we already know fats in your blood can contribute to cholesterol and can lead to the narrowing of your arteries, we think this is an additional part of the puzzle that hasn’t been known about. It could be a double-edged sword. You could get blood fats (lipids) which narrow the blood vessels, but also fatty acids which cause the clots to form or to be more difficult to break down.”
This research is increasing understanding of why the complications that come with diabetes might be happening
There is already some evidence that people with higher levels of fatty acids are more likely to develop blood clots. Now Dr Stewart’s team is running a BHF-funded study, taking blood samples from patient volunteers and measuring their clotting properties. They are looking at whether blood from people with diabetes is more likely to clot, and also whether blood from people with higher levels of fatty acids is more likely to clot.
Dr Stewart says: “We have already seen that when we add zinc to the blood samples, it makes clots thicker and more difficult to break down. The next step is to see in the patient samples if we can directly correlate high levels of fatty acids with clotting.”
Dr Alan Stewart with BHF-funded researchers at St Andrews. (L-R) Amelie Sobczak, Dr Samantha Pitt, Gavin Robertson, Alex Rowley MSP, Dr Siavash Khazaipoul, Roger Mullin, Dr Alan Stewart, Prof David Crossman, Willie Rennie MSP, Kylie Barclay.
Although more research would be needed, it could pave the way to looking at whether existing drugs that reduce fat levels in the blood – such as statins and fibrates – could reduce the risk of blood clots, especially in people with diabetes or cancer.
“We are looking at two sides: the fatty acids and how they affect zinc uptake, and also the role of zinc in blood clotting. We are trying to bring this all together.
A lot of the success we've had has come from that initial BHF grant in 2010
“This research is increasing awareness of fatty acids in the blood and clot formation. It’s increasing understanding of why the complications that come with diabetes might be happening.”
There is still more to learn about what happens to zinc that would normally bind to albumin in your blood, if fatty acids didn’t get in the way. The researchers want to look at other conditions too, such as diabetic retinopathy, which is eye disease that occurs as a complication of diabetes. It’s caused by damage to blood vessels in the retina. Dr Stewart says: “We think this might be caused by tiny micro-clots in the blood vessels of the retina and that the fatty acids in the blood might play a role.”
Dr Stewart says that funding from the BHF has been vital to his research. “In 2010 I was awarded a BHF grant for a PhD student, Omar Kassaar, and that was a very important grant in getting our work in this area started. Based on that work I was able to get other grants, including the BHF project grant and studentship grants which are currently running. A lot of the success we've had has come from that initial BHF grant.”